Cross-Talk of Cells in the Heart 2025 meeting

Cardiac fibroblast-myocyte crosstalk in hyperglycaemic and hypertensive conditions

Introduction

Heart Failure with preserved Ejection Fraction (HFpEF), is a multifactorial disease associated with hypertension, diabetes and obesity, and is predominantly observed in females¹. HFpEF results in a slowly relaxing, fibrotic myocardium, and modifications in cardiomyocyte (CM) Ca²⁺-handling-proteins are observed in animal models in vivo². However, how patient comorbidities may influence cardiac fibroblasts (CFs) and how this may then influence myocytes in the HFpEF phenotype remains unclear. This study aims to develop an in vitro model -which includes aspects of HFpEF to explore abnormal Ca²⁺-signalling of CFs and CMs in hyperglycaemic-hypertensive conditions.

Methods

Adult human male and female CFs (Promocell) and primary left ventricular CMs isolated from adult NZW male rabbits, were cultured independently or co-cultured using media containing 22mM Glucose (HG), 200nM Angiotensin-II (AngII) or a combination of both (to mimic diabetes, hypertension or HFpEF, respectively), for a duration of 24h. Both cell types were then loaded with 2µM Cal520AM calcium indicator. CFs were chemically stimulated using 20nM Endothelin-1 while CMs were electrically field-stimulated at 1Hz to generate Ca²⁺-responses. The alterations in intracellular Ca²⁺ were measured by confocal microscopy.

Results

The Ca²⁺ transient amplitude (ΔF/F₀) in CFs was enhanced with 22mM Glucose (HG) [Control: 0.158±0.015; HG: 0.273±0.014; n=3 humans with 3 technical replicates each; p< 0.001]. The Ca²⁺-transient-amplitude in CMs increased with AngII [Control: 0.750±0.101; Hypertension: 2.02±0.32; N=3 rabbits; p< 0.0001]. In myocytes co-cultured with female CFs, the Ca²⁺-transient-amplitude was sustained with HG and AngII [Control: 0.346±0.064; HG: 0.359±0.049; Ang: 0.296±0.037; N=3 rabbits]. However, Ca²⁺-spark-frequency (sparks.µm².s^-1) in CMs was elevated after co-culture with female CFs, across all pathological conditions [Control: 3.56±0.71; Diabetes: 13.0±1.1; Hypertension: 16.5±1.1; HFpEF: 22.9±1.2; N=3 rabbits; p< 0.001].

Conclusions

These findings show remodelling of Ca²⁺-signalling in CFs and CMs, in an in vitro model of HFpEF. A sex disparity observed in female co-culture mimics that seen in human HFpEF. Further work is needed to understand how this in vitro model correlates to an in vivo model of HFpEF.

Cardiomyocyte microdomains: how local control of submembrane complexes drives cellular communication

Cell-to-cell communication in cardiomyocytes is mediated by specific signalosomes, protein complexes that play essential roles in regulating cellular responses. Cardiomyocytes are highly structured cells, and one key example of microdomain organization is the formation of a functional complex between β2-adrenergic receptors (β₂ARs) and L-type Ca²⁺ channels (LTCCs) on the plasma membrane. However, the functional consequences of this microdomain localization remain incompletely understood. We found that LTCC activity is regulated by proximity coupling mechanisms exclusively via β₂ARs—not β₁ARs—highlighting a specific role for β₂ARs in modulating LTCC response to adrenergic stimulation under healthy conditions. This coupling is lost in heart failure, both in rodent models and in humans, and is dependent on caveolin-3.

Cardiomyocytes also release nerve growth factor (NGF), which guides sympathetic neurons (SN) to form specialized contact sites with cardiomyocytes, termed neuro-cardiac junctions (NCJs). The formation of these NCJ microdomains induces significant physiological changes in cardiac cells. Using a co-culture model of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and SN, we demonstrated that SNs promote functional maturation of hPSC-CMs in vitro. Co-culture resulted in increased structural elongation, enhanced sarcomere organization, and improved force-frequency relationships—key features of mature cardiomyocyte function. Nicotine stimulation elicited a norepinephrine-dependent βAR response from SNs, leading to elevated cAMP production and enhanced contraction and Ca²⁺ transient amplitudes at baseline. Notably, this functional maturation did not extend to metabolic pathways.

Furthermore, SN co-culture increased action potential amplitude and depolarization velocity in hPSC-CMs, supporting a role for SNs in promoting electrophysiological maturation. Our findings suggest that neurons may influence cardiomyocyte expression of channels and receptors, including βARs, LTCCs, and Na⁺ channels (NaCh). We developed a novel patch-clamp technique that enables recording of voltage-gated channels in the cell-attached configuration on specific membrane regions, including the NCJ. Our data show that NCJs are enriched in NaCh-ankyrin G complexes, likely serving as anchoring structures between neurons and cardiomyocytes. The presence of NCJs also increased the number of LTCC/caveolin-3 complexes, suggesting that innervation actively reshapes the functional and electrophysiological landscape of cardiomyocytes.

In conclusion, our work underscores the critical role of submembrane protein complexes in both healthy and pathological cardiac states and highlights how NCJ formation drives functional changes mediated by these complexes.

Validation of a mouse model of early chronic kidney disease-associated cardiomyopathy

Introduction

Chronic kidney disease (CKD) affects 10–15% of the population globally ^[1]. Reduced kidney function can lead to CKD-associated cardiomyopathy, characterized by increased left ventricular mass, diastolic and systolic dysfunction, arrhythmias, and cardiac fibrosis. Our research shows that even individuals with moderate renal impairment exhibit cardiac structural changes^[2] and are at risk of arrhythmias. Despite its high morbidity and mortality, CKD-associated cardiomyopathy remains poorly understood. This study explores the early mechanistic drivers of CKD-associated cardiomyopathy using a murine model induced by an adenine-rich diet.

Methods

8–12-week-old C57BL/6 mice were fed normal chow (male n=9, female n=9) or a 0.15% adenine diet (male n=16, female n=9) for up to 7 weeks. Blood plasma creatinine and urea were measured at sacrifice to assess kidney dysfunction. Kidney and cardiac tissue weights were recorded, and fibrosis was evaluated using histology and collagen 1 western blots. An O-link Target 48 proteomic cytokine panel assessed changes in serum levels of 45 cytokines.

Results

Adenine diet at 7 weeks significantly increased urea (p < 0.0001) in both males (adenine 27.91±5.385 mmol/L vs. control 8.84±0.786 mmol/L) and females (adenine 25.80±2.480 mmol/L vs. control 8.39±0.318 mmol/L). Creatinine also saw a significant increase (p < 0.0001) in both adenine males (adenine 48.89±3.434 umol/L vs. control 10.43±2.159 umol/L) and females (adenine 53.00±5.279 umol/L vs. control 14.86±1.184 umol/L). Kidney weight significantly decreased (p<0.001) in adenine-fed males (104.2 ± 4.600 mg) and females (190.2 ± 11.20 mg) compared to controls (155.8 ± 6.565 mg and 260.9 ± 8.957 mg, respectively). No significant changes in heart-to-body weight ratio were observed in adenine-fed mice (5.489 ± 0.3302 mg/g) compared to controls (5.307 ± 0.1096 mg/g). Histological evidence of fibrosis was observed in the right atrium (4.869 ± 0.5893% vs. 2.158 ± 0.3725%, p < 0.0001), left ventricle (2.866 ± 0.8118% vs. 0.8257 ± 0.1084%, p < 0.01), and left atrium (2.038 ± 0.2326% vs. 1.258 ± 0.1475%, p < 0.05) compared to controls. Western blots also detected an increased collagen 1 protein expression (p<0.05) in adenine fed mice. 39 of 45 proinflammatory cytokines were elevated in adenine fed mice, including biomarkers associated with cardiomyopathy, such as Ccl5, Ccl11, and Ffgf21.

Conclusion

The adenine diet induced early CKD-associated cardiomyopathy, characterized by cardiac fibrosis and systemic inflammation, without significant changes in heart weight^[3]. Our ongoing work is examining the haemodynamic changes, in vivo ECG and electrical changes in the heart.

Development and characterisation of a 3D epicardial cardiac model

INTRODUCTION: The epicardium provides progenitor cells and paracrine signals crucial for cardiac development and repair (1) . Despite its reported dormant status in adulthood, the adult epicardium reactivates in response to cardiac damage to provide pro-reparatory signals, influencing both cardiomyocytes and endothelial cells (1) . Enhancing the reparative potential of the epicardium represents an interesting novel route of intervention, but the paucity of adult in vitro epicardial models hampers progress (2). Advancing models that integrate epicardial cells with other cardiac cell types will be critical for dissecting cell-cell crosstalk in adults in both homeostasis and disease.

AIMS: Develop a 3D epicardial model, characterise this model using a variety of imaging techniques.

METHODS: This project engineered a multicellular heart spheroid model inclusive of the epicardial layer. Cardioids were formed with cardiomyocytes (rat neonatal or H9C2), fibroblasts (rat neonatal or human), and human endothelial cells in a 12,000:12,000:12,000 ratio. Two epicardioids models were developed that consisted of either 1,000 adult pig epicardial cells (EPDCs) or mouse embryonic epicardial cells (MECs). These ratios were chosen to mimic the in vivo composition. Spheroids were optimized for cell ratio and culture conditions and subsequently characterized via bright field and confocal microscopy. Structural organisation of cell types was determined using immunostaining (CD31,MSLN and connexin-43) and viability was assessed with both live dead staining and metabolic activity assays. To determine activity of cells within the spheroids they were challenged with pro-fibrotic TGF-β1 and hypertrophy stimuli such as phenylephrine (PH) and outcomes were assessed via immunostaining and qPCR.

RESULTS: Spheroids formed most robustly at 1:1:1 ratio of rat fibroblasts and cardiomyocytes, and human endothelial cells in cardiomyocyte media yielded spheroids with no central translucency following 3 days of culture. Addition of 1,000 epicardial cells at time 0 resulted in the most intact epicardial layer, showcased by fluorescence imaging. EPDCs epicardioids were smaller than cardioids (P ≤ 0.05), indicating that epicardial cells confers compactness. CD31 and MSLN staining showcased organized endothelial layering suggestive of coronary-like structures. H9C2 myoblasts viability was preserved in EPDC epicardioids as compared to MEC epicardioids (P ≤ 0.01). MEC epicardioids displayed 59% more endothelial cells compared to cardioids (P ≤ 0.001) and 49% more than EPDC epicardioids (P ≤ 0.01), suggesting a pro-angiogenic role of embryonic epicardial cells. Additionally, adult epicardial cells promoted healthy H9C2 morphology compared to Cardioids. Challenge with TGF-β1 resulted in increased collagen expression, a marker of fibroblast activation and enhanced cellular release, as confirmed by immunostaining and qPCR analysis. PH treatment determined a marked trend of increased nuclear area, indicative of hypertrophy.

DISCUSSION & CONCLUSIONS:

Epicardioids offer a novel platform to study adult epicardial communication with the main cell types of the heart. Recapitulating key aspects of epicardial interaction with myocardial and endothelial populations showcased by the structural organisation of endothelial structures and distinct morphological changes in H9C2 cells the presence of adult epicardial cells. This model enables functional assessment of epicardial influence on cardiac remodelling and may accelerate discovery in cardiac regeneration, drug screening, and disease modelling.

Multicellular Modelling of Tumour Necrosis Factor-α Driven Cardiac Dysfunction in Human Engineered Heart Tissues and Myocardial Slices

Heart failure (HF) represents the end-stage phenotype of various cardiac pathologies, including hypertension, ischemic heart disease, diabetes, and cardiomyopathies. In response to cardiac stress, activation of the innate immune system triggers the secretion of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α). Chronic inflammation contributes to adverse cardiac remodeling and progressive ventricular dysfunction. Animal studies have reported that elevated TNF-α levels are associated with cardiac dilation, fibrosis, and contractile dysfunction (1,2). However, due to species differences, findings from animal models may not always translate directly to humans.

In vitro studies indicate that TNF-α overexpression in human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) induce apoptosis and impair Ca²⁺ cycling. This oxidative stress–driven dysfunction ultimately leads to reduced contractile amplitude (3,4). While such studies provide valuable insight into the effect of TNF-α on CMs, these models lack physiological relevance. hiPSC-CMs exhibit a neonatal-like phenotype, which may respond differently to TNF-α compared to adult CMs. Moreover, in the human heart, CMs are in interaction with non-cardiomyocytes, including fibroblasts (FBs) and endothelial cells (ECs). These cell–cell interactions likely influence CM responses to TNF-α, yet they are often not considered in traditional in vitro models.

This study aims to address that gap by investigating the effect of TNF-α in tri-culture engineered heart tissues (EHTs) and human living myocardial slices (LMS). Briefly, hiPSC-CMs, cardiac FBs, and human cardiac microvascular endothelial cells (hCMVECs) were used to generate EHTs. These were treated with 100 ng/mL TNF-α for one week. EHTs were electrically paced at 1 Hz, Ca²⁺ kinetics were measured using live Ca²⁺ imaging, and contractility was assessed via video-based motion analysis. For statistical analysis, data were tested for normality, and an unpaired t-test was applied.

Human donor hearts were provided by the NHS Blood and Transplant INOAR program (IRAS project ID: 189069), with approval from the NHS Health Research Authority and in compliance with the Governance Arrangements for Research Ethics Committees. LMS were generated from the left ventricle of donor human hearts (dimensions: 8 mm × 8 mm × 0.3 mm). Slices were cultured in chambers—one as a control, and the other treated with TNF-α and electrically stimulated during culture (1 Hz, 10 V, 10 ms pulse duration). After two days, contractile function was assessed. To determine whether TNF-α induces arrhythmogenic activity, LMS were paced at 2 Hz for 30 seconds, followed by a 2-minute pause to monitor for spontaneous contractions.

Our data show that TNF-α–treated EHTs exhibited a significantly higher spontaneous beating rate and reduced contraction amplitude (n=8-10/ p<0.05), although no changes in Ca²⁺ handling were observed. Additional replicates are required to confirm these findings. Consistently, TNF-α–treated LMS showed a significant reduction in active force, increase in passive force and slices developed arrhythmic events (n= 10-12/ p<0.001).

In summary, TNF-α impairs contractile function and induces arrhythmias in both EHT and LMS. These findings underscore the pathological role of TNF-α in human cardiac tissue and emphasize the importance of physiologically relevant platforms to study inflammation-driven heart failure. Further investigation is needed to elucidate the underlying signaling mechanisms and explore potential receptor-specific therapeutic strategies.

Age-Associated Loss of Lymphatic Vessels Promotes Cardiac Inflammation

Introduction: Aging is a major risk factor for cardiovascular diseases. One prominent hallmark of cardiac aging is inflammation. The microcirculatory system and age-related immune cell infiltration has been extensively studied in this context, however, the contribution of the lymphatic vasculature to age-related pathologies remains elusive.

Methods: To assess the cardiac lymphatic system, whole mount light sheet microscopy and confocal imaging was used. Functional alterations were investigated using AAV9 coding for Vegfc or soluble Ft4 were injected into 18-month-old and 3-month-old mice, respectively. Flt4;prox1-CreERT2 mice were used as additional model. Finally, molecular mechanisms were characterized using snRNA-seq on aged AAV9-Vegfc treated mcie.

Results: We examined lymphatic capillary density in old (>20 months) and young (3 months) mouse hearts using LYVE1 and PDPN staining. Aging induced a significant decline in lymphatic vessel density in the sub-endocardial and -epicardial area of aged left ventricles in both genders (0.28±0.08 fold and 0.68±0.03 fold; p<0.05), while the right ventricle showed no change. Dilation of peri-arterial lymphatics was observed in old hearts, indicating lymphatic drainage dysfunction. Cardiac aging was accompanied by increased numbers of CD68+ macrophages, accumulation of fibrinogen and amyloid in the interstitial space, and significant tissue edema (p<0.05). The decline in lymphatic vessels was associated with reduced Vegfc expression (0.72±0.04 fold; p<0.005) in aged hearts.

To establish a causal link, we examined hearts from 3-month-old Flt4;Prox1-CreERT2 mice with defective lymphatic vessels. These mice displayed fibrinogen (1.32±0.08 fold; p<0.05) and CD68+ macrophage (1.58±0.08 fold; p<0.05) accumulation compared to wildtype littermates. Blocking VEGFC signaling in young mice by overexpressing soluble Flt4 impaired cardiac lymphatic capillary density (0.62±0.06 fold; p<0.01), leading to increased macrophage and fibrinogen accumulation (1.69±0.09 fold, 4.60±0.30 fold; p<0.001) and diastolic dysfunction.

We then addressed whether restoring Vegfc expression in old mice rescues age-related cardiac impairment. Inducing Vegfc via AAV9 in aged mice restored cardiac lymphatic density by 3-fold and reduced CD68+ macrophage density by 1.6-fold, without affecting fibrinogen accumulation. However, overexpression of Vegfc lead to cardiac fibrosis and transiently impaired diastolic function.

Conclusion: Our study demonstrates an age-related reduction in left ventricular lymphatic density, cardiac edema, and inflammation. Vegfc overexpression prevented age-dependent decline of lymphatic vasculature and reduced cardiac inflammation.

The role of small extracellular vesices in myocardial hypoxia-reoxygenation injury studied with living myocardial slices

Extracellular vesicles (EVs) play a regulatory role in the progression of cardiovascular disease. Myocardial ischaemia-reperfusion injury (IRI) induces an increase in the secretion of small extracellular vesicles (sEVs) in the cardiac microenvironment and peripheral circulation(1). sEVs are lipid bilayer particles within the size range of 35-200nm and secreted by all cell types. Their high content of bioactive molecules – primarily microRNA – is altered in response to external stimuli, leading to behavioral changes of the recipient cells. Studies have shown that cultured cardiomyocytes (CMs) produce exosomes that monitor cardiovascular events in response to IRI in a murine model(2). sEVs produced by stem cell-derived endothelial cells subjected to hypoxia carried a miR that inhibited apoptosis and stimulated angiogenesis, increasing CM survival and contractility in a human IRI heart-on-a-chip model(3).

The mechanism behind altered sEV secretion and their changes in content in cardiovascular disease had not been determined due to lack of models. The human living myocardial slice (LMS) in vitro model maintains the cellular complexity of the myocardium, providing a platform for the isolation of sEVs and allowing the investigation of the changes in sEV concentration and content(4).

The present work aims to employ a new LMS model of IRI to characterize the process of sEV secretion and uptake, and the consequences on the functional, structural and biochemical properties of the myocardium. Human donor hearts are provided by the NHS Blood and Transplant INOAR program with approval from the NHS Health Research Authority (IRAS project ID: 189069), and in compliance with the Governance Arrangements for Research Ethics Committees. The LMSs are subjected to continuous electrical stimulation (1 Hz) and mechanical load (preload 22% stretch); they are exposed to hypoxia-reoxygenation injury (HRI) by being placed in a hypoxic chamber set at 1% O₂ concentration for 2 hours, followed by 24 hours of reoxygenation. After culture, a force transducer is used to measure contraction kinetics at different stretches of the LMS. sEVs are isolated by size exclusion chromatography and their concentration is determined by Nanoparticle Tracking Analysis. Statistical analysis is performed with a 2-way ANOVA with Tukey’s multiple comparisons test.

LMSs subjected to HRI at 1% O₂ for 2 hours show a significant reduction in force transient amplitude at 20%, 22%, 25%, and 30% sarcomere length (p=0.0109, p=0.0039, p=0.003, p=0.002 respectively, N=4) compared to healthy LMSs. In fact, the force transient amplitude of the HRI LMSs decreases by 47% (p<0.0001). Additionally, the quantification of sEVs shows a significant increase in sEV concentration following HRI (p=0.0454, N=4). Future plans include the immunohistochemistry staining of the LMS HRI and sEVs, and the molecular analysis of the microRNA content of sEVs. In summary, the exposure of human LMSs to 1% hypoxia for 2 hours followed by 24 hours reoxygenation affects their function and induces the increased secretion of sEVs.

In conclusion, we have established a reliable human LMS model to investigate the role of sEVs in response to HRI. The molecular analysis of sEV content will allow identification of novel biomarkers and potential therapeutic targets of cardiovascular disease.

Redefining catecholaminergic polymorphic ventricular tachycardia (CPVT) as a neurocardiac condition

Background:

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome caused by mutations in RYR2 (encoding ryanodine receptor 2, RyR2). Investigation into the pro-arrhythmic effects of these mutations have focused exclusively on cardiomyocytes. However, RyR2 is also present in neuronal tissue. Moreover, patients often present with clinical signs of autonomic nervous system (ANS) dysfunction, and treatment strategies frequently target the ANS.

Objective:

To assess whether RyR2 mutations affect the neurons that modulate cardiac function and/or impact on cardiac innervation, using an established CPVT mouse model (RyR2-R2474S).

Methods:

RNA sequencing, immunocytochemistry, live-cell fluorescence imaging, immunohistochemistry and liquid chromatography–mass spectrometry.

Results:

Analysis of published RNA sequencing datasets revealed that RyR2 is abundantly expressed in mouse stellate ganglia (SG; crucial autonomic modulators of cardiac function). Using immunocytochemistry, we confirm the presence of RyR2 protein in these peripheral, cardiac-modulating neurons. Functional investigation revealed a reduction of caffeine-induced calcium release in isolated CPVT SG neurons (Fura Red AM F/F0 CPVT 0.53±0.01 vs wild type (WT) 0.45±0.01; p<0.01), indicating the occurrence of intracellular calcium leakage. Moreover, cultured CPVT SG neurons showed increased neurite outgrowth (βIII tubulin/DAPI-positive area CPVT 6.9±0.6 vs WT 4.1±0.6 µm²; p<0.01). Immunohistochemical staining of mouse heart cryosections with tyrosine hydroxylase (TH) demonstrated a significant increase in the density of sympathetic neuron innervation in ventricular tissue of CPVT mice (TH-positive area CPVT 3.8±0.5 vs WT 1.8±0.4 µm²; p<0.01), and increased innervation heterogeneity (CPVT 5.4±1.3 vs WT 2.3±0.5 Δ µm²; p<0.05). Neurotransmitter quantification in ventricular tissue revealed reduced levels of epinephrine in CPVT hearts (CPVT 0.023±0.002 vs WT 0.041±0.005 nmol/g; p<0.01), elevated levels of the norepinephrine (NE) metabolite normetanephrine (NMN), and a consequent increase in the NMN/NE ratio, which is an index of NE turnover (CPVT 0.26±0.02 vs WT 0.16±0.01 nmol/g; p<0.05). Quantification of blood plasma neurotransmitter metabolites revealed an increase in the dopamine metabolite 3-MT (CPVT 2.4±0.3 vs WT 1.3±0.2 nmol/g; p<0.05).

Conclusion:

The neurons that modulate cardiac function abundantly express RyR2. The RyR2-R2474S mutation leads to significant alterations of stellate ganglia neuron calcium homeostasis, increased neurite outgrowth, sympathetic hyperinnervation and increased innervation heterogeneity of ventricular myocardium, and alterations of cardiac neurotransmitters and their metabolites. These functional and structural alterations of the ANS would have important consequences for cardiac function and arrhythmogenesis and may provide a novel blood biomarker for improved risk stratification and treatment design.

Neurocardiac interactions using hiPSC derived cardiomyocytes and sympathetic neurones from CPVT patients

Background: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a rare but life-threatening inherited arrhythmic disorder, typically triggered by exercise or emotional stress, and a leading cause of sudden cardiac death in the young. CPVT is commonly caused by mutations in calcium-handling components of sarcoplasmic reticulum (SR), which promote diastolic calcium leakage and increase arrhythmogenic risk under adrenergic stress. Current therapies such as β-blockers and, in more severe cases, cardiac sympathetic denervation, remain insufficient in a significant subset of patients – suggesting a more complex pathophysiological mechanism. Although previous studies have characterised CPVT phenotypes in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), the contribution of diseased sympathetic neurones (SNs) to the CPVT phenotype remains poorly understood.

Method: hiPSCs derived from both a CPVT patient and a healthy control were differentiated into cardiomyocytes (hiPSC-CMs) and sympathetic neurones (hiPSC-SNs). Electrophysiological activity was assessed using multi-electrode array (MEA) recordings. Calcium transients were measured using Fura-2AM indicator. Real time cAMP dynamics were monitored using a fluorescence resonance energy transfer (FRET) based biosensor (Epac-S^H187). All hiPSC lines used in this study were ethically approved and obtained from established sources with appropriate donor consent.

Results: To characterise features of baseline cardiac action potential, MEA measurements were conducted. At baseline, 47% (8 out of 17) of CPVT hiPSC-CMs exhibited spontaneous arrhythmic activity, including tachycardia and re-entry phenomena, compared to none in controls (n=8). Among regularly beating cells, CPVT hiPSC-CMs showed significantly shorter RR intervals (control: 0.5638±0.049s, n=8; vs CPVT: 0.4412±0.025s, n=8; unpaired t-test; p<0.05) and field potential durations (control: 0.3406±0.041s, n=8; vs CPVT: 0.1844±0.015s, n=8; unpaired t-test; p<0.01). Application of isoprenaline (β-adrenergic stimulation) shortened RR interval in both groups. Arrhythmias were triggered in some CPVT cardiomyocytes (regular at baseline), but not in controls. Calcium imaging revealed greater isoprenaline-induced calcium transients in CPVT hiPSC-CM (Control: 0.05±0.01, n=11; vs CPVT: 0.99±0.13, n=14; unpaired t-test, p<0.05). Spontaneous calcium discharges were detected in 77.4% (24 out of 31) of CPVT compared to 10% (1 out of 10) of controls. FRET analysis showed significantly elevated cAMP responses in CPVT hiPSC-CM following isoprenaline stimulation (control: 48.63±1.625%, n=98; vs CPVT: 64.25±1.990%, n=70; Mann-Whitney test; p<0.0001). For hiPSC-SN, CPVT displayed enhanced calcium transients and elevated cAMP elevation following nicotine stimulation, compared to isogenic controls. In hiPSC neurocardiac co-culture, nicotine stimulation increased the beating rate of cardiomyocytes, confirming functional connectivity. The reduction in RR interval was significantly greater in control cardiomyocytes co-cultured with CPVT neurones (n=5) than with control neurones (n=4, Mann-Whitney test; p<0.05). Calcium imaging showed that CPVT hiPSC-SN consistently exhibited elevated calcium transients, regardless of cardiomyocyte genotype they were paired with. This indicates that hyperactivity of neurones is intrinsic and not modulated by co-cultured cardiomyocytes.

Conclusion: Our investigation confirms hallmark CPVT abnormalities in hiPSC-CMs, including arrhythmia, calcium dysregulation and altered β-adrenergic cAMP signalling. Additionally, our results suggest a novel pathogenic role for CPVT sympathetic neurones, whose intrinsic hyperactivity exacerbates the cardiomyocyte phenotype via neurocardiac cross-talk. These findings provide new insights into the pathophysiology of CPVT and highlight the potential of targeting sympathetic excitability as a therapeutic strategy for personalised treatments.

Aging-Induced Sympathetic Hyperinnervation is Specific to the Left Atrium

Introduction: With increasing life expectancy, age-related diseases emerged as a leading cause of mortality. The aging myocardium is characterized by structural/functional alterations, which predispose the elderly to arrhythmias. The autonomic nervous system (ANS) and neurovascular interactions recently gained increasing attention, as previous findings demonstrate that endothelial senescence induced denervation of the left ventricle (LV) in aging. However, the effects of aging on atrial innervation and neurovascular cross-talks remains unexplored. Since alterations of the ANS increases the risk of atrial fibrillation (AFib), which is highly prevalent in the elderly, we explored the innervation and the neuro-vascular cross-talk in the aging atria.

Aims/Objectives: In this project we aim to study age-related changes in atrial innervation and possible impact on arrhythmias.

Methods: To characterize the ageing murine atria, we used immunofluorescence-based stainings and senolytic experiments. Further, we included single-nuclei RNA sequencing and in vivo electrical pacing experiments. Burst stimulation protocol for atria was used to provoke atrial arrhythmias.

Results: To investigate atrial innervation in aged hearts, we stained pan-neuronal marker beta-3-tubulin in LAs of 3-months-old and 22-months-old mice, observing a 1.6±0.1-fold increase (p=0.0141 (unpaired, parametric t-test), 3m n=8, 22m n=6)) in aged mice, while innervation decreased in the LV. This increase in LA innervation was primarily attributed to enhanced sympathetic innervation, with a 1.6±0.1-fold increase (p=0.0003 (unpaired, parametric t-test), 3m n=13, 22m n=8)) as determined by tyrosine-hydroxylase staining.

Since we previously found that vascular senescence controls denervation of the LV, we investigated cellular senescence patterns between the LV and the LA. Acid β-galactosidase staining showed a 3.4±0.1-fold increase (p=0.001 (unpaired, parametric t-test), 3m n=11, 22m n=8) in LA senescence with age. However, double staining with cell type specific markers revealed no increase in endothelial cell senescence but a tendency for increased senescence in CD45-positive immune cells (2.7±0.1-fold increase, p=0.0964 (unpaired, parametric t-test), n=8) and CD68-positive macrophages (2.9±0.1-fold increase, p=0.0585 (unpaired, parametric t-test), n=8).

Consistent with these findings, treating mice with the endothelial cell specific senolytic drug fisetin did not affect LA senescence or hyperinnervation in aged LAs after 2 months of treatment but reduced cellular senescence in the LV. These data indicate that LA hyperinnervation in aging is associated with immune cell but not endothelial cell senescence.

To investigate mechanisms underlying LA hyperinnervation, we performed single-nuclei RNA sequencing. First analyses demonstrate that macrophages show an increased neuroinflammation signature in aged murine LAs. Cell types like endocardial endothelial cells on the other hand showed a more pro-axon guidance phenotype with declined axon-repelling factors such as SEMA3A, while protective factors such as VEGFB were increased.

Preliminary results of electrical pacing experiments in young and 16-months-old mice revealed that aged mice have a higher susceptibility for induced AFib compared to young counterparts. This suggests that LA hyperinnervation might be associated with AFib. Histological analysis of LA samples from human patients (n=3) confirmed high innervation levels in AFib.

Conclusions: In conclusion, we demonstrate hyperinnervation in aged LAs. Future research will focus on the relationship between AFib and LA hyperinnervation while unraveling the molecular mechanisms driving these age-related changes.

Investigating the role of IKs and IKr in the electrophysiological responses to sympathetic nerve stimulation in an innervated isolated rabbit heart model

Introduction

Sympathetic nerve stimulation(SNS) shortens ventricular action potential duration(APD), ensuring diastolic filling despite increased heart rate(HR). This shortening has been reported to be driven by sympathetically sensitive I_Ks and I_Kr currents. SNS is known to increase the risk of sudden cardiac death through an increased incidence of ventricular fibrillation(VF) linked to the heterogenous effects of SNS on ventricular electrophysiology caused by regional differences in nerve and ion channel distribution. The effects of I_Kr and I_Ks blockade on this heterogeneity, and on the electrophysiological effects of SNS, have not been studied in detail in the rabbit ventricle.

Methods

An innervated isolated rabbit (NZW 3.38± 0.05kg, initial sedation (subcutaneous Sedator-0.2mg/kg, Ketavet-10mg/kg), followed by surgery under intravenous propofol before terminal anaesthesia (Dolethal – 160mg/kg)) was used to examine left ventricular (LV) APD responses to SNS during pacing. Protocols were run initially without drug, followed by pharmacological blockade of I_Ks(0.5μM HMR, n=6) or I_Kr(0.03μM E4031, n=7) and finally with blockade of both I_Kr and I_Ks combined(0.5μM HMR and 0.03μM E4031)

Results

Both LV apical and basal APDs were lengthened by E4031 (110±5ms to 133±5ms, p<0.001; 118±5ms to 146±10ms, p<0.05) and were modestly but not significantly lengthened with HMR (118±3ms to 127±5ms;119±7ms to 128±5ms). Similarly, both LV apical and basal APDs were lengthened significantly by the addition of E4031 to HMR (140±6ms, p<0.01; 163±8ms, p<0.01), and more modestly by the addition of HMR to E4031(150±11ms; 151±10ms). In all cases, SNS shortened both apical and basal APD, but the magnitude of this SNS-induced shortening was almost always greater in the base.

The effective refractory period (ERP) was also lengthening with HMR and to a greater extent with E4031(135±4ms to 146±4ms, p<0.01; 127±6 to 170±8ms, p<0.01). SNS significantly shortened ERP both in the absence and presence of HMR (120±4ms, p<0.001; 131±7ms, p<0.01) and E4031(116±3ms, p<0.05; 145±6ms, p<0.01). While the magnitude of this SNS-induced shortening was the same with or without HMR(-10.7% to -10.4%), it was significantly increased by E4031(-8.1% to -14.6%, p<0.5). ERP was not compared with both drugs combined, as the protocol often induced ventricular fibrillation(6/16 hearts).

Despite the high incidence of VF during ERP protocols with both drugs we saw no significant changes in VFT with HMR, E4031 or both drugs combined. In addition, the magnitude of the SNS-induced reduction in VFT was not significantly altered by these pharmacological blockades.

Conclusion

In this study, we observed greater APD and ERP lengthening with E4031 than with HMR and an increase in SNS-induced ERP shortening only with E4031. These results reflect the known variation in the roles of I_Ksand I_Kr in both the rabbit ventricle and in the sympathetic response. Despite a noticeable increase in the incidence of VF with both drugs combined during our ERP protocol, we didn’t observe any significant changes in VFT in this study, perhaps a result of the protocol used. In addition, when both I_Kr and I_Kswere pharmacologically blocked, the SNS-induced APD shortening and VFT reduction were still present, suggesting that in these experiments, some repolarisation reserve remains.

Generation of an engineered heart tissue model of Hypertrophic Cardiomyopathy, caused by MYBPC3 R820W mutation

Introduction: Hypertrophic cardiomyopathy (HCM) is a disease that affects 3 in 20 cats and 1 in 500 humans [1]. The MYBPC3 R820W mutation causes HCM in ragdoll cats and humans [2], and is characterised by cardiomyocyte (CM) remodelling, myofiber disarray, interstitial fibrosis, left ventricular hypertrophy and hypercontractility. Despite some breakthrough drugs such as Mavacamten, there are limited treatments available to reverse all aspects of HCM, such as interstitial fibrosis [3]. The exact pathological mechanisms leading to HCM caused by the MYBPC3 R820W mutation have not been studied in detail. However, they likely involve interactions between dysfunctional CMs and other cardiac cells, including cardiac fibroblasts (CFs) [4, 5]. Our lab has generated a novel induced pluripotent stem cell (iPSC) line homozygous mutant for the MYBPC3 R820W mutation (R820W+/+), and an isogenic control line.

Our overall aim for this project was to generate an engineered heart tissue (EHT) model of HCM and use it to understand the aberrant interactions between R820W+/+ iPSC-derived CMs (iPSC-CMs) and CFs. Our objectives were:

To use a novel ImageJ and R script to measure differences in contractility parameters between EHT groups.
To use immunohistochemistry to measure differences in iPSC-CM area (hypertrophy), iPSC-CM alignment and fibrosis.

Methods: We generated EHTs containing R820W+/+ or isogenic control iPSC-CMs, either alone or with CFs (n=5-10 per group). EHTs were cultured for 2 weeks, then electrically stimulated at 1Hz and 10 second videos were taken to measure contractility. Then EHTs were either fixed for staining or processed for RNA and protein extraction. Two-way ANOVA was used for all statistical analyses.

Results: EHTs with CFs showed a significantly shorter time to peak of contraction and contraction duration compared to EHTs with iPSC-CMs only, regardless of iPSC-CM mutation (p<0.0001 isogenic control, p=0.0093 R820W+/+). R820W+/+ EHTs with iPSC-CMs only had a significantly shorter time to peak of contraction compared to isogenic control EHTs with iPSC-CMs only (p=0.0363). Also, R820W+/+ EHTs with iPSC-CMs and CFs had a significantly shorter relaxation time, compared to the R820W+/+ EHTs with iPSC-CM only. For iPSC-CM area, results revealed a larger iPSC-CM area in R820W+/+ EHTs with CFs, compared to isogenic control EHTs with CFs. For iPSC-CM alignment, we found that adding CFs to isogenic control EHTs caused significantly more iPSC-CM alignment, compared to isogenic control EHTs with iPSC-CMs only (p<0.0001). Also, R820W+/+ EHTs with CFs showed significantly less iPSC-CM alignment, compared to the isogenic control EHTs with CFs (P=0.0186). Analysis of Masson’s trichrome staining showed no significant difference in fibrosis between groups (P>0.05).

Conclusions: our model of HCM shows a mild hypercontractile phenotype, which is ameliorated by the addition of CFs. Our results also show the expected interactions between isogenic control iPSC-CMs and CFs, indicating that the model is working. We have revealed a possible interaction between R820W+/+ iPSC-CMs and CFs which leads to hypertrophy and myocardial disarray. Future work will focus on investigating differences at the protein and gene level, and maturing the EHT model further with electrical stimulation in culture.

L-type calcium channel regulation by β2AR in a coculture model of innervated cardiomyocytes

Introduction. L-Type calcium channels (LTCC) are an essential element in the excitation-contraction coupling of cardiomyocytes (CMs). Recently, we have shown that the regulation of the LTCC activity by proximity coupling mechanisms occurs only via β₂AR, but not β₁AR, with the requirement of caveolin 3 (Cav3) to form complexes (1). We hypothesise that this mechanism can play a role in tuning the LTCC response by β₂ARs under sympathetic stimulation. This study aims to investigates how sympathetic innervation regulates CM adrenergic responses, the effect of innervation on the formation of an LTCC/β₂ARs/Cav3 complex(es), and what impact innervation has in driving arrhythmogenic events.

Methods. CMs and sympathetic neurons (SNs) were isolated from neonatal rat pups and cocultured for periods of 3-4 and 7-10 days. Methods ranged from contraction analysis and Ca²⁺ transient with either β₁AR or β₂AR antagonists by high-throughput multicellular CytoCypher, scanning ion conductance microscopy (SICM), smart patch-clamp, and immunostaining confocal imaging. All experiments were performed under Imperial College London ethical guidelines.

Results. CytoCypher contraction analysis shows how the role of innervation matures over time in culture. At 4 days, innervated CMs show no remarkable differences from non-innervated. However, at 8 days, innervated CMs shows a higher peak of contraction (0.332±SEM, n=19) than non-innervated (0.175±SEM, n=22). Interestingly, using β₁AR and β₂AR blockers on contracting cells show an overall decrease in time to peak and time to baseline in both innervated and non-innervated, suggesting a competitive role between βAR in our culture conditions. Single channel patch clamp analysis suggest that innervation doubles the open probability of LTCCs (innervated: 0.089, n=4, p=0.0571 vs non-innervated: 0.046, n=4). Through immunostaining of LTCC and Cav3 proteins, we show the presence of LTCC/Cav3 complexes, with a higher co-localisation coefficient on innervated CMs than non-innervated (p=0.0076). Arrhythmia analysis under nicotine stimulation showed that only innervated CMs under β₂AR blockage are more susceptible to arrhythmias than any other group tested at both time points (4-day, n=4-5, p=0.0005; and 8-day, n=3-4 p<0.0001 versus control).

Conclusion. Our preliminary results suggest that β₂AR plays an important role in the control of CM contraction by sympathetic innervation. Specifically, our results suggest that innervated CMs may have a higher number of LTCC complexes associated with Cav3 and β₂AR, and they may be essential in mitigating CM susceptibility to arrhythmias.

Intracellular Ca2+ and circadian rhythms in pro-arrhythmic activity of rat pulmonary vein cardiomyocytes.

Introduction.

Episodes of atrial fibrillation (AF) in patients tend to occur at night. Cardiomyocytes in the pulmonary vein (PV) sleeves are a major source of the ectopic activity driving AF. The pulmonary vein sleeves are highly innervated and it is known that the autonomic nervous system plays a role in the onset of AF. In addition, spontaneous diastolic Ca²⁺ release has been suggested to play a role in the generation of delayed afterdepolarisations (DADs), triggered activity and abnormal automaticity in PV cardiomyocytes.

Aims/objectives.

This study addresses the hypothesis that 24-hr variation in Ca²⁺ release plays a role in circadian rhythms in proarrhythmic activity of PV cardiomyocytes.

Methods.

Animal procedures were approved by the Animal Welfare and Ethics Review Board of the University of Bristol and conducted in accordance with UK law. Male Wistar rats were maintained in a 24-hr cycle of 12-hr light/dark (lights-on at Zeitgeber time, ZT=0; lights-off, ZT12). Hearts were removed under terminal general anaesthesia at 4 times (ZT, Zeitgeber Times) through the 24-hour cycle (ZT 0, 6, 12, 18). Whole-cell current clamp recordings were made from cardiomyocytes isolated from the proximal PV (n=75 cells) and the left atrial appendage (LAA, n=65 cells) of 16 rats and loaded with Cal520-AM (5 μM). The frequency and amplitude of DADs, and diastolic spontaneous Ca release transients (spCaT) were measured and the effects of the cardiac sympathetic neurotransmitter, noradrenaline (NA, 1 µM), examined. DAD and spCaT amplitude and frequency were plotted against ZT of recording and fitted with a sine wave. Fitted curves were compared using an extra-sum-of-squares F-test (P<0.05).

Results and Discussion.

Under control conditions, DADs and spCaT could be recorded in both PV and LAA cardiomyocytes, with the frequencies and amplitudes being greatest during the resting phase (ZT0-12) compared to the active phase (ZT12-24) in both cell types. However, DAD/spCaT frequencies and amplitudes were generally greater in PV than in LAA cardiomyocytes in both rest and active phases. Superfusion with NA increased DAD and spCaT frequency and amplitude in both cell types with the greatest effects during the resting phase and in PV cardiomyocytes. DAD amplitude was closely correlated with spCaT amplitude in both cell types, with the slope of the relation being greater in PV than LAA cardiomyocytes and being increased markedly by NA. There was a ZT-dependence to the slope of the DAD amplitude/spCaT relation under control conditions and in the presence of NA.

Conclusions.

Taken together, these data suggest a role for noradrenergic control of diastolic spontaneous Ca²⁺ release in the circadian rhythms in proarrhythmic activity of PV cardiomyocytes.

Neural regulation of cardiac pericytes – a novel mechanism for cardiac regeneration

Background: Cardiac regeneration after myocardial infarction (MI) critically depends on the restoration of blood flow to the affected area. Angiogenesis, driven by the dynamic interaction between endothelial cells and pericytes, is therefore pivotal for the cardiac recovery after MI. Abundant in the heart’s dense capillary network, pericytes regulate vascular tone, modulate immune responses, and play a key role in vessel formation, maturation, and stabilization. Leveraging their regenerative and angiogenic properties offers a promising strategy to ischemic heart repair. Myocardial infarction is associated with autonomic imbalance, characterised by reduced vagal activity. Restoring cholinergic input through vagus nerve stimulation has been shown to exert anti-arrhythmic effects, reduce infarct size, promote angiogenesis, and favour myocardial functional recovery. Despite the recognized importance of neurally derived trophic factors in cardiac regeneration, this aspect remains largely underexplored.

Aim: To explore the potential interplay between autonomic neural regulation and pericytes in cardiac regeneration following MI.

Methods: Human cardiac pericytes are isolated from cardiac surgery waste tissue, expanded in vitro and treated with carbachol (cholinergic agonist) or isoprenaline (b-adrenergic agonist) every 24h at rising concentrations. Cell viability is assessed at 24, 48 and 72h using calcein/EthDIII, while proliferation is evaluated using EdU incorporation after 48h of treatment. To measure cell migration speed and efficiency, wound healing assay is used, and migration is observed during a 24-hour period. Immunocytochemistry is employed to investigate the expression of neurotransmitter receptors. To mimic ischemic conditions in vitro, pericytes are cultured under hypoxia and deprived of growth factors for 24h.

Results: At tested concentrations, neither drug had adverse effects on cardiac pericyte viability or morphology. Preliminary data indicate that neither carbachol nor isoprenaline influences cardiac pericyte proliferation. However, both drugs were found to enhance pericyte migration induced by PDGF-BB. Immunostaining revealed that pericytes express neurotransmitter receptors associated with cardioprotection, including α7 nicotinic and M3 muscarinic acetylcholine receptor.

Conclusion:These findings suggest that autonomic neurotransmitters may enhance pro-angiogenic function of pericytes, supporting the notion that neural modulation contributes to myocardial regeneration. Ongoing studies will further characterize neuroactivated pericytes and downstream signaling pathways involved in vascular repair, guiding future regenerative therapies.

New submission

Sodium-glucose cotransporter 2 inhibitors attenuate left atrial electrical remodelling induced by high-fat diet

Rina Sha1, Olivia Baines1, Abbie Hayes1, Sophie Broadway-Stringer1, Manish Kalla1,3, Ming Lei4, Katja Gehmlich1, Andrew P Holmes1,2, Christopher O’Shea1, Davor Pavlovic1

1 Cardiovascular Sciences, University of Birmingham, UK. 2 Institute of Clinical Sciences, University of Birmingham, UK. 3 Department of Cardiology, Queen Elizabeth Hospital, UK. 4 Department of Pharmacology, University of Oxford, UK.

Introduction:

Obesity significantly increases the risk of developing atrial arrhythmias. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally used for diabetes management, have shown potential anti-arrhythmic benefits, though their direct effects on atrial cardiac electrophysiology in the setting of obesity are unclear. Our work aims to define the atrial proarrhythmic alterations induced by high-fat diet (HFD) and to test if early treatment with SGLT2 inhibitors can attenuate observed changes.

Methods:

CD1 mice (5–8 weeks old) were randomised into three groups: normal chow, HFD, and HFD + SGLT2 inhibitor. The normal chow group received standard chow and water for 20 weeks. The HFD group were fed HFD and high-fructose (15%) water for 20 weeks. During the last

six weeks, the HFD + SGLT2 inhibitor group received dapagliflozin (3 g/kg/day) in their drinking water. ECGs and echocardiography were performed at weeks 14 and 20. At 20 weeks, blood and urine samples were collected to measure glucose levels. An Olink® Target 48 proteomic cytokine panel was used to assess changes in protein expression of 45 key cytokines in plasma. Left atrial electrical activity was assessed using cardiac optical mapping, measuring action potential duration (APD) and conduction velocity (CV). Effective refractory

periods (ERP) were assessed using an S1-S2 pacing protocol. Optical mapping data analysis was performed with ElectroMap.

Results:

After 20 weeks, the HFD and HFD+SGLT2 inhibitor groups showed significantly greater body weight gain than the normal chow group (28.32 ± 2.66, 25.89 ± 3.45, and 9.43 ± 0.93 g, respectively; p < 0.0001). As expected, the HFD + SGLT2 inhibitor group showed glucose in

their urine. No differences were observed in left atrial weight, blood glucose, cytokine biomarkers or ECG parameters. Interestingly, the SGLT2 inhibitor group showed increased left ventricular wall thickness (Anterior: 1.413 ± 0.0793, 1.525 ± 0.0539, 1.600 ± 0.0781mm, respectively. p>0.05. Posterior: 1.624 ± 0.0861, 1.683 ± 0.0757, 1.952 ± 0.0929mm, respectively. p<0.05). HFD induced substantive pro-arrhythmic changes in the left atria. HFD shortened APD at 30%, 50% and 80% repolarisation (APD30, APD50, APD80), decreased ERP and slowed left atrial CV, compared to the normal chow group. SGLT2 inhibitors attenuated the repolarisation deficits, by increasing APD30, APD50 and APD80 while reducing APD heterogeneities and attenuated the HFD-induced ERP changes (57.60 ± 3.92, 42.40 ± 3.12, 47.40 ± 3.41ms, respectively; p > 0.05).

Conclusions:

HFD induces pro-arrhythmic changes in murine left atria. Interestingly, this occurs in the absence of changes in systemic cytokine/inflammatory markers. SGLT2 inhibitors exhibited substantive anti-arrhythmic effects by modulating cardiac electrophysiology. These findings suggest that early treatment with SGLT2 inhibitors may prevent obesity-induced atrial electrical remodelling. Further studies in obese animal models and patients are warranted to explore their therapeutic role in arrhythmia prevention.

Membership category	Early registration rate until 25 July 2025	Standard registration rate until 13 August 2025
Undergraduate/Master’s member	£150.00	£230.00
Postgraduate member	£150.00	£230.00
Full member (concessionary) *	£150.00	£230.00
Full member	£220.00	£300.00
Fellow member	£220.00	£300.00
Honorary Fellow	£220.00	£300.00
Retired member	£150.00	£230.00
Non-member	£440.00	£540.00
ECR Non-member *	£300.00	£400.00

Registration opens	26 February 2025
Abstract submission opens	26 March 2025
Abstract submission closes	02 June 2025
Early bird registration deadline	25 July 2025
Conference Attendance Award deadline	31 July 2025
Registration deadline	13 August 2025
Meeting dates	3 – 4 September 2025

Become a member

Check out our Training Hub

What is physiology?

Meet our members

Advancing Physiology Together: Showcasing Research, Enhancing Careers, and Building Communities

Wednesday 03 September - Thursday 04 September 2025

Cross-Talk of Cells in the Heart 2025: Novel Mechanisms of Disease and Arrhythmias

Date

Location

10:00 SA01 Cardiac fibroblast-myocyte crosstalk in hyperglycaemic and hypertensive conditions

10:30 SA02 Cardiomyocyte microdomains: How local control of submembrane complexes drives cellular communication

11:30 C01 Validation of a mouse model of early chronic kidney disease-associated cardiomyopathy

11:45 C02 Development and characterisation of a 3D epicardial cardiac model

12:00 C03 Multicellular modelling of tumour necrosis factor-α driven cardiac dysfunction in human engineered heart tissues and myocardial slices

14:00 Atrial cardiomyopathy and inflammatory processes in the atria

14:30 SA03 Regional specific changes in cardiac resident macrophages and fibroblasts modulate long-term atrial fibrillation maintenance

15:00 C04 Age-associated loss of lymphatic vessels promotes cardiac inflammation

15:15 C05 The role of small extracellular vesicles in myocardial hypoxia-reoxygenation injury studied with living myocardial slices

16:00 Neurocardiac interaction in malignant ventricular arrhythmias and sudden cardiac death

16:30 SA04 Redefining catecholaminergic polymorphic ventricular tachycardia (CPVT) as a neurocardiac condition

17:00 C06 Neurocardiac interactions using hiPSC derived cardiomyocytes and sympathetic neurones from CPVT patients

17:15 C07 Aging-induced sympathetic hyperinnervation is specific to the left atrium

17:30 C08 Investigating the role of IKs and IKr in the electrophysiological responses to sympathetic nerve stimulation in an innervated isolated rabbit heart model

17:45 The application of mapping systems

09:00 SA05 Neurocardiac interactions in the human heart: Defining heart highways

09:30 Leveraging engineered cardiac tissues to study secreted biomarkers in heart cell interactions

10:00 SA06 “Disease in a dish” models to understand the mechanisms of atrial fibrillation in cardiomyopathies

10:30 C09 Generation of an engineered heart tissue model of hypertrophic cardiomyopathy, caused by MYBPC3 R820W mutation

10:45 Physiological data acquisition in cardiovascular research

11:30 Uncovering mechanisms promoting atrial fibrillation in heart failure

12:00 SCN5A beyond the cardiomyocyte: role in cardiac arrhythmogenesis

12:30 C10 L-type calcium channel regulation by β2AR in a coculture model of innervated cardiomyocytes

12:45 C11 Intracellular Ca2+ and circadian rhythms in pro-arrhythmic activity of rat pulmonary vein cardiomyocytes

14:45 Understanding the intra-cardiac adipose-cardiomyocyte communication axis

15:15 Weight loss reverses left atrial electrical remodelling associated with obesity in mice fed high-fat diet

15:45 C12 Neural regulation of cardiac pericytes – a novel mechanism for cardiac regeneration

16:00 C13 Sodium-glucose cotransporter 2 inhibitors attenuate left atrial electrical remodelling induced by high-fat diet

Registration

Member registration

Non-member registration

Applying for a visa

Abstracts

Key Information

Key dates

Venue

Travel

Support to Attend

Grants for Carers

Conference Attendance Award

Partner With Us

Partner Packages

Site search

Filter

Content Type

17:30 C08 Investigating the role of IKs and IKr in the electrophysiological responses to sympathetic nerve stimulation in an innervated isolated rabbit heart model