Pub Date : 2025-12-21DOI: 10.1016/j.yjmcc.2025.12.007
Dogacan Yücel , Calvin Smith , Natalia Ferreira de Araujo , Fernando Souza-Neto , Upendra Chalise , Grace Schuler , Bayardo I. Garay , Jennifer L. Mikkila , Omar Atef Abdelhamid Mahmoud , Pratima Mandal , Verena Höffken , Joachim Kremerskothen , Rita C.R. Perlingeiro , Jop H. van Berlo
{"title":"Corrigendum to ‘Small-scale siRNA screen reveals WWC2 as a novel regulator of cardiomyocyte mitosis’ [Journal of Molecular and Cellular Cardiology 210 (2025) 127–136]","authors":"Dogacan Yücel , Calvin Smith , Natalia Ferreira de Araujo , Fernando Souza-Neto , Upendra Chalise , Grace Schuler , Bayardo I. Garay , Jennifer L. Mikkila , Omar Atef Abdelhamid Mahmoud , Pratima Mandal , Verena Höffken , Joachim Kremerskothen , Rita C.R. Perlingeiro , Jop H. van Berlo","doi":"10.1016/j.yjmcc.2025.12.007","DOIUrl":"10.1016/j.yjmcc.2025.12.007","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Page 131"},"PeriodicalIF":4.7,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-20DOI: 10.1016/j.yjmcc.2025.12.009
Haoqi Li , Huimin Li , Yufan Chao , Yaozhao Li , Zijie Cheng , Yuqing Li , Yun Yin , Tao Chen , Xin Dong , Dan Wu , Qingxun Hu
Redox homeostasis is crucial for cellular function and signaling, with its disruption linked to various diseases. Given the compartment-specific nature of redox regulation, we employed highly responsive genetically encoded fluorescent sensors, including Hyper7, iNap, and roGFP2, to achieve real-time in situ tracking of the redox dynamics of H2O2, NADPH and GSH in the cytoplasm and mitochondria. It revealed that glycolysis and oxidative phosphorylation differentially modulate redox metabolites across subcellular domains, demonstrating metabolic pathway-specific regulation of redox equilibrium. Pathological modeling (cardiac hypertrophy, ischemia-reperfusion and cuproptosis) characterized mitochondrial redox systems exhibit superior stress-responsive regulation versus cytoplasmic counterparts, displaying enhanced dynamic responses during injury progression. These results suggest that precise subcellular redox mapping delivers critical insights into dynamic signal transduction mechanisms and proposes targeted therapeutic avenues for redox-associated pathologies through compartment-specific interventions.
{"title":"Biosensors reveal subcellular redox status in live cells","authors":"Haoqi Li , Huimin Li , Yufan Chao , Yaozhao Li , Zijie Cheng , Yuqing Li , Yun Yin , Tao Chen , Xin Dong , Dan Wu , Qingxun Hu","doi":"10.1016/j.yjmcc.2025.12.009","DOIUrl":"10.1016/j.yjmcc.2025.12.009","url":null,"abstract":"<div><div>Redox homeostasis is crucial for cellular function and signaling, with its disruption linked to various diseases. Given the compartment-specific nature of redox regulation, we employed highly responsive genetically encoded fluorescent sensors, including Hyper7, iNap, and roGFP2, to achieve real-time in situ tracking of the redox dynamics of H<sub>2</sub>O<sub>2</sub>, NADPH and GSH in the cytoplasm and mitochondria. It revealed that glycolysis and oxidative phosphorylation differentially modulate redox metabolites across subcellular domains, demonstrating metabolic pathway-specific regulation of redox equilibrium. Pathological modeling (cardiac hypertrophy, ischemia-reperfusion and cuproptosis) characterized mitochondrial redox systems exhibit superior stress-responsive regulation versus cytoplasmic counterparts, displaying enhanced dynamic responses during injury progression. These results suggest that precise subcellular redox mapping delivers critical insights into dynamic signal transduction mechanisms and proposes targeted therapeutic avenues for redox-associated pathologies through compartment-specific interventions.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"212 ","pages":"Pages 1-9"},"PeriodicalIF":4.7,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.yjmcc.2025.12.005
Yang Zhou , Xiao-Ping Xie , Bo-Lai Shen , Ao Wang , Bo-Wen Li , Zhi-Wei Wang
Background
Aortic dissection (AD) is a life-threatening cardiovascular condition characterized by high morbidity and mortality rates. However, the molecular mechanism of intracellular pH in AD development has not been fully elucidated. In this study, the role of carbonic anhydrase 9 (CA9) in VSMCs intracellular pH and the regulatory mechanism were investigated.
Methods
Cell viability was examined by cell counting kit-8 (CCK-8) and intracellular pH was detected by BCECF-AM probe. The regulation of CA9 transcription by HIF-1α was measured by Cut &run-qPCR assay. The levels of CA9, HIF-1α, MMP2 and α-SMA were evaluated by RT-qPCR, Western blot and Immunofluorescence.
Results
Our results demonstrated that CA9 was significantly upregulated in AD tissues, primarily localized in VSMCs, and associated with increased MMP2 levels, while α-SMA levels decreased. Silencing CA9 in VSMCs resulted in reduced cell viability and increased intracellular pH. Additionally, we found that HIF-1α was upregulated in AD, regulating CA9 expression in VSMCs. Treatment with JTC801 in a BAPN-induced mouse model reduced CA9 and HIF-1α expression, improving survival and decreasing AD incidence.
Conclusion
This study establishes CA9 as a hypoxia-responsive mediator of pH dysregulation in AD, modulated by HIF-1α. Targeting the HIF-1α/CA9 axis with JTC801 presents a novel therapeutic strategy to restore VSMC homeostasis and ECM integrity. These findings advance our understanding of intracellular pH in AD and highlight this approach may be a potential therapeutic target.
{"title":"JTC801 inhibited CA9 activation via HIF-1α to promotes alkaliptosis in vascular smooth muscle cells and alleviate the formation of aortic dissection","authors":"Yang Zhou , Xiao-Ping Xie , Bo-Lai Shen , Ao Wang , Bo-Wen Li , Zhi-Wei Wang","doi":"10.1016/j.yjmcc.2025.12.005","DOIUrl":"10.1016/j.yjmcc.2025.12.005","url":null,"abstract":"<div><h3>Background</h3><div>Aortic dissection (AD) is a life-threatening cardiovascular condition characterized by high morbidity and mortality rates. However, the molecular mechanism of intracellular pH in AD development has not been fully elucidated. In this study, the role of carbonic anhydrase 9 (CA9) in VSMCs intracellular pH and the regulatory mechanism were investigated.</div></div><div><h3>Methods</h3><div>Cell viability was examined by cell counting kit-8 (CCK-8) and intracellular pH was detected by BCECF-AM probe. The regulation of CA9 transcription by HIF-1α was measured by Cut &run-qPCR assay. The levels of CA9, HIF-1α, MMP2 and α-SMA were evaluated by RT-qPCR, Western blot and Immunofluorescence.</div></div><div><h3>Results</h3><div>Our results demonstrated that CA9 was significantly upregulated in AD tissues, primarily localized in VSMCs, and associated with increased MMP2 levels, while α-SMA levels decreased. Silencing CA9 in VSMCs resulted in reduced cell viability and increased intracellular pH. Additionally, we found that HIF-1α was upregulated in AD, regulating CA9 expression in VSMCs. Treatment with JTC801 in a BAPN-induced mouse model reduced CA9 and HIF-1α expression, improving survival and decreasing AD incidence.</div></div><div><h3>Conclusion</h3><div>This study establishes CA9 as a hypoxia-responsive mediator of pH dysregulation in AD, modulated by HIF-1α. Targeting the HIF-1α/CA9 axis with JTC801 presents a novel therapeutic strategy to restore VSMC homeostasis and ECM integrity. These findings advance our understanding of intracellular pH in AD and highlight this approach may be a potential therapeutic target.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"212 ","pages":"Pages 75-88"},"PeriodicalIF":4.7,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.yjmcc.2025.12.006
Ming Ding , Li Zheng , Tapan A. Patel , Matthew C. Zimmerman , Kaushik P. Patel , Paul L. Sorgen
Hypoxia induces pathological remodeling in cardiomyocytes, in part by disrupting gap junction communication through Connexin43 (Cx43) phosphorylation and internalization. Here, we identify Proline-rich tyrosine kinase 2 (Pyk2) as a critical mediator of hypoxia- and adrenergic-induced Cx43 remodeling and cardiomyocyte dysfunction. Neonatal rat ventricular myocytes exposed to hypoxia (1 % O₂) for 1 or 24 h exhibited increased expression of hypoxia-inducible factor 1α and activated Pyk2 (pY402 and pY579/580), without changes in the total level of Pyk2. Hypoxia also enhanced Cx43 phosphorylation at Y265, a Pyk2-specific site, and increased expression of GJA1–20 k, an alternatively translated Cx43 isoform that supports Cx43 trafficking and mitochondrial function. Pharmacological Pyk2 inhibition with PF4618433 prevented hypoxia-induced Pyk2 activation, Cx43 phosphorylation, and attenuated the increase in GJA1–20 k expression. Immunofluorescence analysis revealed that hypoxia reduced Cx43 localization at intercellular junctions, an effect reversed by PF4618433 treatment. Functionally, Pyk2 inhibition reduced cell damage, as reflected by lower lactate dehydrogenase release and improved contractile activity. Mechanistically, PF4618433 attenuated apoptosis, oxidative stress, and preserved mitochondrial membrane potential, consistent with improved mitochondrial function. Furthermore, norepinephrine-induced Pyk2 activation and Cx43 Y265 phosphorylation were comparably suppressed by PF4618433, linking Pyk2 to both hypoxic as well as adrenergic stress signaling in cardiomyocytes. These findings demonstrate that Pyk2 activation promotes Cx43 downregulation, contributing to cardiomyocyte injury under hypoxic and adrenergic stress. Inhibition of Pyk2 preserves gap junction integrity, maintains mitochondrial function, and enhances cell survival, supporting Pyk2 as a promising therapeutic target in cardiac injury.
{"title":"Inhibition of Pyk2 prevents Cx43 remodeling and cardiomyocyte injury during hypoxic and adrenergic stress","authors":"Ming Ding , Li Zheng , Tapan A. Patel , Matthew C. Zimmerman , Kaushik P. Patel , Paul L. Sorgen","doi":"10.1016/j.yjmcc.2025.12.006","DOIUrl":"10.1016/j.yjmcc.2025.12.006","url":null,"abstract":"<div><div>Hypoxia induces pathological remodeling in cardiomyocytes, in part by disrupting gap junction communication through Connexin43 (Cx43) phosphorylation and internalization. Here, we identify Proline-rich tyrosine kinase 2 (Pyk2) as a critical mediator of hypoxia- and adrenergic-induced Cx43 remodeling and cardiomyocyte dysfunction. Neonatal rat ventricular myocytes exposed to hypoxia (1 % O₂) for 1 or 24 h exhibited increased expression of hypoxia-inducible factor 1α and activated Pyk2 (pY402 and pY579/580), without changes in the total level of Pyk2. Hypoxia also enhanced Cx43 phosphorylation at Y265, a Pyk2-specific site, and increased expression of GJA1–20 k, an alternatively translated Cx43 isoform that supports Cx43 trafficking and mitochondrial function. Pharmacological Pyk2 inhibition with PF4618433 prevented hypoxia-induced Pyk2 activation, Cx43 phosphorylation, and attenuated the increase in GJA1–20 k expression. Immunofluorescence analysis revealed that hypoxia reduced Cx43 localization at intercellular junctions, an effect reversed by PF4618433 treatment. Functionally, Pyk2 inhibition reduced cell damage, as reflected by lower lactate dehydrogenase release and improved contractile activity. Mechanistically, PF4618433 attenuated apoptosis, oxidative stress, and preserved mitochondrial membrane potential, consistent with improved mitochondrial function. Furthermore, norepinephrine-induced Pyk2 activation and Cx43 Y265 phosphorylation were comparably suppressed by PF4618433, linking Pyk2 to both hypoxic as well as adrenergic stress signaling in cardiomyocytes. These findings demonstrate that Pyk2 activation promotes Cx43 downregulation, contributing to cardiomyocyte injury under hypoxic and adrenergic stress. Inhibition of Pyk2 preserves gap junction integrity, maintains mitochondrial function, and enhances cell survival, supporting Pyk2 as a promising therapeutic target in cardiac injury.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Pages 119-130"},"PeriodicalIF":4.7,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1016/j.yjmcc.2025.11.010
Eliza Sassu , Gavin Tumlinson , Dragana Stefanovska , Marbely C. Fernández , Pia Iaconianni , Josef Madl , Tomás A. Brennan , Manuel Koch , Breanne A. Cameron , Sebastian Preissl , Ursula Ravens , Franziska Schneider-Warme , Peter Kohl , Callum M. Zgierski-Johnston , Luis Hortells
{"title":"Corrigendum to “Age-related structural and functional changes of the intracardiac nervous system” Journal of Molecular and Cellular Cardiology, Volume 187 (2024) 1–14]","authors":"Eliza Sassu , Gavin Tumlinson , Dragana Stefanovska , Marbely C. Fernández , Pia Iaconianni , Josef Madl , Tomás A. Brennan , Manuel Koch , Breanne A. Cameron , Sebastian Preissl , Ursula Ravens , Franziska Schneider-Warme , Peter Kohl , Callum M. Zgierski-Johnston , Luis Hortells","doi":"10.1016/j.yjmcc.2025.11.010","DOIUrl":"10.1016/j.yjmcc.2025.11.010","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Pages 92-93"},"PeriodicalIF":4.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145723911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1016/j.yjmcc.2025.12.004
Marine Cacheux , Benjamin Strauss , Shestruma Parajuli , Aymen Halouani , Michael G. Katz , Seun Imani , Samar Antar , Nestor Bedoya , Lahouaria Hadri , Fadi G. Akar , Yassine Sassi
Pulmonary Arterial Hypertension (PAH), a major cause of right ventricular failure, is associated with a high 5-year mortality rate. Arrhythmias account for a significant proportion of morbidity and mortality in PAH patients. Hence, there is a critical need for new therapies to effectively treat PAH-related cardiac arrhythmias. The purpose of this study was to evaluate the efficacy of extracellular cyclic adenosine monophosphate (e-cAMP) treatment in reversing pathophysiological electrophysiological (EP) remodeling and arrhythmia propensity caused by PAH. Ex-vivo optical action potential (AP) mapping, real-time reverse transcription–polymerase chain reaction, immunostaining, morphological and histologic analyses were performed on two different models of pulmonary hypertension (Monocrotaline and Sugen/pneumonectomy) to test the impact of e-cAMP treatment in suppressing ventricular arrhythmias in PAH. PAH diseased rats from both models exhibited a high propensity of inducible ventricular tachycardia (VT). Remarkably, e-cAMP treatment suppressed the incidence of VT in both models. Examination of the EP substrate revealed action potential duration prolongation and marked conduction slowing in PAH-diseased animals. These features, however, were significantly reversed by e-cAMP treatment. Moreover, e-cAMP reversed the development of AP alternans in PAH. Extracellular cAMP-treated rats exhibited a significant decrease in myocardial fibrosis and hypertrophic remodeling. Reversal of EP remodeling by e-cAMP was accompanied by decreased pulmonary vascular remodeling and by restored cardiac expression of key ion channel transcripts. Extracellular cAMP treatment reduces the incidence of ventricular arrhythmias and suppresses pathological EP remodeling by restoring cardiac and pulmonary vascular remodeling. This approach may represent a new therapeutic modality for arrhythmia suppression in PAH patients.
{"title":"Extracellular-cAMP suppresses pulmonary arterial hypertension-induced ventricular arrhythmias","authors":"Marine Cacheux , Benjamin Strauss , Shestruma Parajuli , Aymen Halouani , Michael G. Katz , Seun Imani , Samar Antar , Nestor Bedoya , Lahouaria Hadri , Fadi G. Akar , Yassine Sassi","doi":"10.1016/j.yjmcc.2025.12.004","DOIUrl":"10.1016/j.yjmcc.2025.12.004","url":null,"abstract":"<div><div>Pulmonary Arterial Hypertension (PAH), a major cause of right ventricular failure, is associated with a high 5-year mortality rate. Arrhythmias account for a significant proportion of morbidity and mortality in PAH patients. Hence, there is a critical need for new therapies to effectively treat PAH-related cardiac arrhythmias. The purpose of this study was to evaluate the efficacy of extracellular cyclic adenosine monophosphate (e-cAMP) treatment in reversing pathophysiological electrophysiological (EP) remodeling and arrhythmia propensity caused by PAH. Ex-vivo optical action potential (AP) mapping, real-time reverse transcription–polymerase chain reaction, immunostaining, morphological and histologic analyses were performed on two different models of pulmonary hypertension (Monocrotaline and Sugen/pneumonectomy) to test the impact of e-cAMP treatment in suppressing ventricular arrhythmias in PAH. PAH diseased rats from both models exhibited a high propensity of inducible ventricular tachycardia (VT). Remarkably, e-cAMP treatment suppressed the incidence of VT in both models. Examination of the EP substrate revealed action potential duration prolongation and marked conduction slowing in PAH-diseased animals. These features, however, were significantly reversed by e-cAMP treatment. Moreover, e-cAMP reversed the development of AP alternans in PAH. Extracellular cAMP-treated rats exhibited a significant decrease in myocardial fibrosis and hypertrophic remodeling. Reversal of EP remodeling by e-cAMP was accompanied by decreased pulmonary vascular remodeling and by restored cardiac expression of key ion channel transcripts. Extracellular cAMP treatment reduces the incidence of ventricular arrhythmias and suppresses pathological EP remodeling by restoring cardiac and pulmonary vascular remodeling. This approach may represent a new therapeutic modality for arrhythmia suppression in PAH patients.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Pages 109-118"},"PeriodicalIF":4.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145723899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.yjmcc.2025.12.003
Yongjun Wang , Shane R. Zhao , Dong Han , Wenshu Zeng , Mohamed Rafiuddin Ahmed , Xulei Qin , Qiang Liu , Joe Z. Zhang , Jayakumar Rajadas , Joseph C. Wu
{"title":"Galangin alleviates cardiac ischemia/reperfusion injury in human iPSC-derived cardiomyocytes and animal models","authors":"Yongjun Wang , Shane R. Zhao , Dong Han , Wenshu Zeng , Mohamed Rafiuddin Ahmed , Xulei Qin , Qiang Liu , Joe Z. Zhang , Jayakumar Rajadas , Joseph C. Wu","doi":"10.1016/j.yjmcc.2025.12.003","DOIUrl":"10.1016/j.yjmcc.2025.12.003","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Pages 94-97"},"PeriodicalIF":4.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.yjmcc.2025.12.001
Alexandre Lewalle , Gregory Milburn , Jania Bell , Kenneth S. Campbell , Steven A. Niederer
In humans, the left atria (LA) and the left ventricle (LV) play distinct physiological roles and express sarcomeric proteins with chamber-specific patterns. Despite these important differences, most multi-chamber descriptions of the heart assume uniform myocardial properties. To facilitate a more accurate representation of cardiac function, we measured and compared the contractile properties of isolated skinned human LA and LV muscle fibers at 37 . Our experimental measurements included the length-dependent activation (LDA) of force in the isometric steady state, the force response to small quick length changes, and tension redevelopment dynamics. The LV measurements display more pronounced LDA behavior compared to LA, whereas the LA dynamics is generally faster than LV.
To elucidate these differences mechanistically, we used the LA and LV experimental datasets to fit a biophysical model framework to produce a representative model for each chamber. Our Bayesian statistical approach aimed to maximize the objectivity of the model calibrations and to allow a systematic assessment of chamber-specific parameter differences. Passive mechanical properties emerge as the principal determinant of LDA behavior. However, variations in cross-bridge cycling kinetics account more significantly for LA/LV differences in the ATP consumption to produce a given isometric force.
These results constitute the first systematic biophysical comparison of LA and LV cardiomyocyte contraction mechanics in humans, paving the way to further investigation of their roles within the broader cardiovascular physiological context.
{"title":"Human atrial skinned muscle fibers exhibit reduced length-dependent activation but show faster force development kinetics than ventricular muscle","authors":"Alexandre Lewalle , Gregory Milburn , Jania Bell , Kenneth S. Campbell , Steven A. Niederer","doi":"10.1016/j.yjmcc.2025.12.001","DOIUrl":"10.1016/j.yjmcc.2025.12.001","url":null,"abstract":"<div><div>In humans, the left atria (LA) and the left ventricle (LV) play distinct physiological roles and express sarcomeric proteins with chamber-specific patterns. Despite these important differences, most multi-chamber descriptions of the heart assume uniform myocardial properties. To facilitate a more accurate representation of cardiac function, we measured and compared the contractile properties of isolated skinned human LA and LV muscle fibers at 37 <span><math><mrow><mo>°</mo><mi>C</mi></mrow></math></span>. Our experimental measurements included the length-dependent activation (LDA) of force in the isometric steady state, the force response to small quick length changes, and tension redevelopment dynamics. The LV measurements display more pronounced LDA behavior compared to LA, whereas the LA dynamics is generally faster than LV.</div><div>To elucidate these differences mechanistically, we used the LA and LV experimental datasets to fit a biophysical model framework to produce a representative model for each chamber. Our Bayesian statistical approach aimed to maximize the objectivity of the model calibrations and to allow a systematic assessment of chamber-specific parameter differences. Passive mechanical properties emerge as the principal determinant of LDA behavior. However, variations in cross-bridge cycling kinetics account more significantly for LA/LV differences in the ATP consumption to produce a given isometric force.</div><div>These results constitute the first systematic biophysical comparison of LA and LV cardiomyocyte contraction mechanics in humans, paving the way to further investigation of their roles within the broader cardiovascular physiological context.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Pages 64-77"},"PeriodicalIF":4.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.yjmcc.2025.12.002
Hanna J. Tadros , Diwakar Turaga , Kyle Hope , Joseph A. Spinner , Iki Adachi , Xiao Li , James F. Martin
Non-ischemic cardiomyopathy (NICM) is a devastating diagnosis with a wide array of phenotypes, ranging from mild cardiac hypertrophy to end-stage heart failure. Single-cell/nucleus RNA sequencing technologies have expanded and become a necessary tool to unravel the transcriptome across thousands to millions of cells. Studies incorporating these technologies to examine pediatric and adult myocardium have improved our understanding of underlying pathophysiology in cardiomyopathy, identified novel gene and genetic pathway associations, and paved the way for precision medicine therapeutics in cardiovascular medicine. We compiled the recent literature that showcase single cell/nucleus technologies in NICM in adult and pediatric populations and describe cell type-specific changes, ultimately setting the stage for future targeted gene manipulation/precision medicine.
{"title":"Single cell transcriptomic landscape of adult and pediatric non-ischemic cardiomyopathy","authors":"Hanna J. Tadros , Diwakar Turaga , Kyle Hope , Joseph A. Spinner , Iki Adachi , Xiao Li , James F. Martin","doi":"10.1016/j.yjmcc.2025.12.002","DOIUrl":"10.1016/j.yjmcc.2025.12.002","url":null,"abstract":"<div><div>Non-ischemic cardiomyopathy (NICM) is a devastating diagnosis with a wide array of phenotypes, ranging from mild cardiac hypertrophy to end-stage heart failure. Single-cell/nucleus RNA sequencing technologies have expanded and become a necessary tool to unravel the transcriptome across thousands to millions of cells. Studies incorporating these technologies to examine pediatric and adult myocardium have improved our understanding of underlying pathophysiology in cardiomyopathy, identified novel gene and genetic pathway associations, and paved the way for precision medicine therapeutics in cardiovascular medicine. We compiled the recent literature that showcase single cell/nucleus technologies in NICM in adult and pediatric populations and describe cell type-specific changes, ultimately setting the stage for future targeted gene manipulation/precision medicine.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Pages 98-108"},"PeriodicalIF":4.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1016/j.yjmcc.2025.11.015
David Sánchez-López , David García-Vega , J.E. Viñuela , Isabel Ferreirós-Vidal , Diego Iglesias-Álvarez , José Manuel Martínez-Cereijo , Laura Reija-López , Ángel L. Fernández-González , José R. González-Juanatey , Sonia Eiras
{"title":"Corrigendum to ‘FABP4, marker of worse prognosis in cardiovascular disease, induces neutrophil’s proatherogenic phenotype which is modulated by semaglutide’ [Journal of Molecular and Cellular Cardiology volume 210 (2026) 12–27]","authors":"David Sánchez-López , David García-Vega , J.E. Viñuela , Isabel Ferreirós-Vidal , Diego Iglesias-Álvarez , José Manuel Martínez-Cereijo , Laura Reija-López , Ángel L. Fernández-González , José R. González-Juanatey , Sonia Eiras","doi":"10.1016/j.yjmcc.2025.11.015","DOIUrl":"10.1016/j.yjmcc.2025.11.015","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Page 63"},"PeriodicalIF":4.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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