Journal of molecular and cellular cardiology最新文献

{"title":"Biosensors reveal subcellular redox status in live cells","authors":"Haoqi Li ,&nbsp;Huimin Li ,&nbsp;Yufan Chao ,&nbsp;Yaozhao Li ,&nbsp;Zijie Cheng ,&nbsp;Yuqing Li ,&nbsp;Yun Yin ,&nbsp;Tao Chen ,&nbsp;Xin Dong ,&nbsp;Dan Wu ,&nbsp;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 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.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"212 ","pages":"Pages 1-9"},"PeriodicalIF":4.7,"publicationDate":"2026-03-01","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}

{"title":"Impaired retinoic acid signaling mediated Rbm20 downregulation induces aberrant splicing of CaV1.2 calcium channel: implications in myocardial hypertrophy","authors":"Xinyu Song ,&nbsp;Dan Yang ,&nbsp;Zhe Sun ,&nbsp;Shumin Yin ,&nbsp;Chenhao Wang ,&nbsp;Wei Hou ,&nbsp;Yu Sun ,&nbsp;Fen Zheng ,&nbsp;Juejin Wang","doi":"10.1016/j.yjmcc.2025.11.011","DOIUrl":"10.1016/j.yjmcc.2025.11.011","url":null,"abstract":"<div><h3>Aims</h3><div>Myocardial hypertrophy, a pathological adaptation to chronic stress, predisposes to heart failure through dysregulated calcium handling. Alternative splicing (AS) of Ca_V1.2 calcium channel participates in myocardial hypertrophy, and RNA-binding motif protein 20 (Rbm20) regulates Ca_V1.2 AS. Moreover, impaired retinoic acid receptor β (RARβ) is implicated in cardiac pathologies, but its roles in handling cardiac intracellular calcium during myocardial hypertrophy remain unknown. Here, we explore whether impaired RARβ exacerbates cardiac pathological remodeling by disrupting Rbm20-mediated Ca_V1.2 AS.</div></div><div><h3>Methods and results</h3><div>Transverse aortic constriction (TAC) and isoproterenol (ISO)-induced murine hypertrophic hearts showed increased Ca_V1.2 alternative exon 9* (Ca_V1.2_E9_*), accompanied with reduced Rbm20 expression. Rbm20 downregulated Ca_V1.2 exon 9* in cardiomyocytes. Bioinformatic analysis of human hypertrophic cardiomyopathy datasets revealed impaired RA signaling, marked by RARβ downregulation, which was confirmed in TAC hearts and ISO-treated neonatal rat ventricular myocytes (NRVMs). RARβ knockdown increased the proportion of Ca_V1.2_E9_* channels and K⁺-triggered intracellular Ca²⁺ concentration ([Ca²⁺]_i) in NRVMs. Chromatin immunoprecipitation and dual-luciferase assays identified that RARβ directly binds to <em>Rbm20</em> promoter region, and adapalene (ADP), a selective RARβ agonist, increased their binding affinity. For clinical relevance, ADP restored Rbm20 expression, normalized Ca_V1.2_E9_* splicing, decreased K⁺-triggered [Ca²⁺]_i, and attenuated cardiomyocyte hypertrophy. In vivo, ADP administration alleviated myocardial hypertrophy in TAC mice.</div></div><div><h3>Conclusion</h3><div>Our findings reveal impaired RARβ drives Ca_V1.2 aberrant splicing by downregulating Rbm20, establishing a feedforward loop of intracellular calcium imbalances and hypertrophic remodeling. Significantly, ADP restores Ca_V1.2 AS and intracellular calcium homeostasis by activating RARβ in cardiomyocytes, highlighting a novel therapeutic approach for myocardial hypertrophy.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Pages 28-42"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582185","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}

{"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 ,&nbsp;Gavin Tumlinson ,&nbsp;Dragana Stefanovska ,&nbsp;Marbely C. Fernández ,&nbsp;Pia Iaconianni ,&nbsp;Josef Madl ,&nbsp;Tomás A. Brennan ,&nbsp;Manuel Koch ,&nbsp;Breanne A. Cameron ,&nbsp;Sebastian Preissl ,&nbsp;Ursula Ravens ,&nbsp;Franziska Schneider-Warme ,&nbsp;Peter Kohl ,&nbsp;Callum M. Zgierski-Johnston ,&nbsp;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":"2026-02-01","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}

{"title":"Cyclic AMP-dependent regulation of ryanodine receptors in healthy and diseased hearts","authors":"Mohit M. Hulsurkar ,&nbsp;Isabelle Ong ,&nbsp;Joshua A. Keefe ,&nbsp;Issam H. Abu-Taha ,&nbsp;Dobromir Dobrev ,&nbsp;Xander H.T. Wehrens","doi":"10.1016/j.yjmcc.2025.11.013","DOIUrl":"10.1016/j.yjmcc.2025.11.013","url":null,"abstract":"<div><div>Cyclic adenosine monophosphate (cAMP) is a critical second messenger in cardiomyocytes, regulating essential cellular functions. Upon G-protein-coupled receptor stimulation, adenylyl cyclase (AC) synthesizes cAMP, which phosphodiesterase (PDE) enzymes subsequently degrade. Recent studies challenge the traditional view of uniform cAMP signaling, revealing nanodomain-specific regulation within cardiomyocytes. This localized cAMP signaling modulates key Ca²⁺-handling proteins, including ryanodine receptor type-2 (RyR2), through channel-bound protein kinases and PDEs. Additionally, nucleoside-diphosphate kinases (NDPKs), particularly NDPK-C, contribute to cAMP synthesis and RyR2 regulation. Elevated NDPK-C levels in failing hearts correlate with increased cAMP levels, enhanced sarcoplasmic reticulum Ca²⁺ release, and cardiac arrhythmias. Furthermore, cAMP influences the expression of Ca²⁺-handling proteins. This review examines the mechanisms governing cAMP levels in the sarcoplasmic reticulum nanodomain and their role in regulating RyR2 function in healthy and diseased hearts.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Pages 53-62"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634615","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}

{"title":"Sphingosine-1-phosphate activates ICl,swell in ventricular myocytes via mitochondrial reactive oxygen production","authors":"Frank J. Raucci ,&nbsp;Adolfo G. Mauro ,&nbsp;Edward J. Lesnefsky ,&nbsp;Clive M. Baumgarten","doi":"10.1016/j.yjmcc.2025.11.009","DOIUrl":"10.1016/j.yjmcc.2025.11.009","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Aims&lt;/h3&gt;&lt;div&gt;We previously demonstrated that bacterial sphingomyelinase (SMase), which converts plasmalemmal sphingomyelin to long-chain ceramides, activates the swelling-activated chloride current (&lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt;) in rabbit ventricular myocytes in a reactive oxygen (ROS)-dependent manner under isosmotic conditions. Ceramides can be converted to sphingosine by ceramidase and, in turn, phosphorylated by sphingosine kinase to yield sphingosine-1-phosphate (S1P), which binds to multiple cytoplasmic targets and activates S1P receptors via inside-out transport. This study was designed to determine the cellular source of ROS production elicited by SMase, the sphingolipid species responsible, and thereby, the mechanism of activation of &lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt; by sphingolipids.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods and results&lt;/h3&gt;&lt;div&gt;Whole-cell patch clamp experiments were conducted using freshly isolated rabbit ventricular myocytes. Inhibition of ceramidase with D-&lt;em&gt;erythro&lt;/em&gt;-MAPP, which increases the concentration of endogenous ceramides in the cell membrane, prevented activation of &lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt; upon exposure to SMase. Similarly, inhibition of sphingosine kinase with DL-&lt;em&gt;threo&lt;/em&gt;-dihydrosphingosine to prevent SIP formation by phosphorylation of sphingosine also completely inhibited SMase-induced Cl&lt;sup&gt;−&lt;/sup&gt; current. In contrast, addition of S1P to the bath solution elicited &lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt;. ROS generated by both NADPH oxidase 2 (NOX2) and mitochondria previously were implicated in triggering &lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt;. SMase-induced &lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt; activation was abrogated by blocking mitochondrial electron transport at Complex I with rotenone but was insensitive to blockade of NOX2 with either apocynin or gp91ds-tat. Moreover, diazoxide, which augments mitochondrial ROS production, evoked &lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt;, and 5-HD, an inhibitor of this pathway, reversed the SMase and diazoxide-induced currents. Flow cytometry using C-H&lt;sub&gt;2&lt;/sub&gt;DCFDA-AM to assess cytoplasmic ROS in HL-1 myocytes confirmed the effects of the interventions on ROS production.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Taken together, these data suggest S1P is the sphingolipid that triggers &lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt; in cardiomyocyte, and activation of &lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt; by SMase and S1P is due to ROS produced by mitochondria and appears independent of NOX2.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Translational perspective&lt;/h3&gt;&lt;div&gt;&lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt; modulates apoptosis, cell volume, action potential duration, and participation in mechanoelectrical feedback in cardiomyocytes. Persistent activation of &lt;em&gt;I&lt;/em&gt;&lt;sub&gt;&lt;em&gt;Cl,swell&lt;/em&gt;&lt;/sub&gt; is seen in several forms of cardiac disease, including dilated cardiomyopathy [&lt;span&gt;&lt;span&gt;1&lt;/span&gt;&lt;/span&gt;] and models of heart failure [&lt;span&gt;&lt;span&gt;2&lt;/span&gt;&lt;/span","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Pages 18-27"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564211","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}

{"title":"Human atrial skinned muscle fibers exhibit reduced length-dependent activation but show faster force development kinetics than ventricular muscle","authors":"Alexandre Lewalle ,&nbsp;Gregory Milburn ,&nbsp;Jania Bell ,&nbsp;Kenneth S. Campbell ,&nbsp;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":"2026-02-01","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}

{"title":"Galangin alleviates cardiac ischemia/reperfusion injury in human iPSC-derived cardiomyocytes and animal models","authors":"Yongjun Wang ,&nbsp;Shane R. Zhao ,&nbsp;Dong Han ,&nbsp;Wenshu Zeng ,&nbsp;Mohamed Rafiuddin Ahmed ,&nbsp;Xulei Qin ,&nbsp;Qiang Liu ,&nbsp;Joe Z. Zhang ,&nbsp;Jayakumar Rajadas ,&nbsp;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":"2026-02-01","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}

{"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 ,&nbsp;David García-Vega ,&nbsp;J.E. Viñuela ,&nbsp;Isabel Ferreirós-Vidal ,&nbsp;Diego Iglesias-Álvarez ,&nbsp;José Manuel Martínez-Cereijo ,&nbsp;Laura Reija-López ,&nbsp;Ángel L. Fernández-González ,&nbsp;José R. González-Juanatey ,&nbsp;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":"2026-02-01","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}

{"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 ,&nbsp;Calvin Smith ,&nbsp;Natalia Ferreira de Araujo ,&nbsp;Fernando Souza-Neto ,&nbsp;Upendra Chalise ,&nbsp;Grace Schuler ,&nbsp;Bayardo I. Garay ,&nbsp;Jennifer L. Mikkila ,&nbsp;Omar Atef Abdelhamid Mahmoud ,&nbsp;Pratima Mandal ,&nbsp;Verena Höffken ,&nbsp;Joachim Kremerskothen ,&nbsp;Rita C.R. Perlingeiro ,&nbsp;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":"2026-02-01","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}

{"title":"Central regulation of the heart in type 2 diabetes mellitus","authors":"Shivani Sethi ,&nbsp;Isaiah Cheong ,&nbsp;Carol T. Bussey ,&nbsp;Daryl O. Schwenke ,&nbsp;Jeffrey R. Erickson ,&nbsp;Colin H. Brown ,&nbsp;Regis R. Lamberts","doi":"10.1016/j.yjmcc.2025.11.012","DOIUrl":"10.1016/j.yjmcc.2025.11.012","url":null,"abstract":"<div><div>Diabetic heart disease is a leading cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). A major yet frequently under-recognized component of diabetic heart disease is cardiac autonomic neuropathy (CAN), a condition characterized by dysregulated sympathetic and parasympathetic drive to the heart.</div><div>Current pharmacological treatments for diabetic CAN are often ineffective, having been extrapolated from other health conditions. These therapies predominantly target the peripheral symptoms of elevated sympathetic activity, whilst largely neglecting its origins in sympathoexcitatory regions of the central autonomic network. Sympathetic control of cardiac function originates from the hypothalamus, medulla oblongata, midbrain, and pons, and is relayed through the intermediolateral cell column of the thoracic spinal cord and the intrinsic cardiac nervous system. Targeting the central autonomic network to modulate cardiac sympathetic drive presents a promising novel therapeutic avenue for the treatment of diabetic CAN.</div><div>This review briefly summarizes established knowledge regarding the pathophysiology and management of diabetic CAN, and the implications of recent findings of increased neuronal activation in central sympathoregulatory regions early in the development of T2DM. Increased cardiac sympathetic in the intital stages of T2DM might represent a novel therapeutic target to reduce the impact of CAN and thereby improve outcomes in patients with T2DM.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"211 ","pages":"Pages 43-52"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573745","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}