Journal of molecular and cellular cardiology最新文献

{"title":"Circadian biology of cardiac aging","authors":"Sharanya S. Bettadapura ,&nbsp;William D. Todd ,&nbsp;Graham R. McGinnis ,&nbsp;Danielle R. Bruns","doi":"10.1016/j.yjmcc.2024.12.001","DOIUrl":"10.1016/j.yjmcc.2024.12.001","url":null,"abstract":"<div><div>The age of the U.S. population is increasing alongside a growing burden of age-related cardiovascular disease. Circadian rhythms are critical for human health and are disrupted with aging and cardiovascular disease. The goal of the present review is to summarize how cardiac circadian rhythms change with age and how this might contribute to the increasing burden of age-associated heart disease. Further, we will review what is known about interventions to slow aging and whether they impact cardiac clock function, as well as whether time-of-day or chronotherapy may improve cardiac function with age. Although much remains to be understood about the circadian biology of cardiac aging, we propose that altered circadian clock output should be considered a hallmark of aging and that efforts to fix the clock are warranted for healthy cardiac aging.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"199 ","pages":"Pages 95-103"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927093","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":"Calpain cleavage of Junctophilin-2 during cardiac stress: The G482/T483 site is not to be blamed","authors":"Long-Sheng Song,&nbsp;Duane D. Hall,&nbsp;Jinxi Wang","doi":"10.1016/j.yjmcc.2024.12.005","DOIUrl":"10.1016/j.yjmcc.2024.12.005","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"199 ","pages":"Pages 60-61"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845950","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":"Optogenetic stimulation and simultaneous optical mapping of membrane potential and calcium transients in human engineered cardiac spheroids","authors":"Bijay Guragain ,&nbsp;Hanyu Zhang ,&nbsp;Yalin Wu ,&nbsp;Yongyu Wang ,&nbsp;Yuhua Wei ,&nbsp;Garrett A. Wood ,&nbsp;Lei Ye ,&nbsp;Gregory P. Walcott ,&nbsp;Jianyi Zhang (Jay) ,&nbsp;Jack M. Rogers","doi":"10.1016/j.yjmcc.2024.12.003","DOIUrl":"10.1016/j.yjmcc.2024.12.003","url":null,"abstract":"<div><div>Optogenetic stimulation combined with optical mapping of membrane potential (Vm) and calcium transients (CaT) is a powerful electrophysiological tool. We developed a novel experimental platform in which tissue is stimulated optogenetically while Vm and CaT are imaged simultaneously. The Vm indicator is an organic dye, while the CaT indicator is genetically encoded. We used cardiac spheroids containing cardiomyocytes and fibroblasts differentiated from human induced pluripotent stem cells as model tissue. The spheroids were genetically encoded with an optogenetic actuator, CheRiff, and the calcium indicator jRCaMP1b. The Vm indicator was the organic dye RH237. CheRiff was excited using blue light (450 nm), and both RH237 and jRCaMP1b were excited using a single band of green light (either 525–575 nm or 558–575 nm). Fluorescence emission was split and imaged by two cameras (CaT: 595–665 nm; Vm: &gt;700 nm). The spheroids were successfully stimulated optogenetically and Vm and CaT were recorded simultaneously without cross-talk using both excitation light bands. The 525–575 nm band produced higher signal-to-noise ratios than the 558–575 nm band, but caused a slight increase in tissue excitability because of CheRiff activation. The optogenetic actuator and CaT indicator are genetically encoded and can be expressed in engineered tissue constructs. In contrast, the Vm indicator is an organic dye that can stain any tissue. This system is well-suited for studying coupling between engineered tissue grafts and host tissue because the two tissue types can be stimulated independently, and tissue activation can be unambiguously attributed to either graft or host.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"199 ","pages":"Pages 51-59"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824255","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":"Deficiency of Sox7 leads to congenital aortic stenosis via abnormal valve remodeling","authors":"Weiqi Feng ,&nbsp;Nanchao Hong ,&nbsp;Yizhuo Wu ,&nbsp;Junxin Huang ,&nbsp;Qi Zhang ,&nbsp;Guizhu Liu ,&nbsp;Ziling Qian ,&nbsp;Yinghui Chen ,&nbsp;Lihui Jin ,&nbsp;Xiaowei Ding ,&nbsp;Pengjun Zhao ,&nbsp;Alex F. Chen ,&nbsp;Yu Yu","doi":"10.1016/j.yjmcc.2024.11.015","DOIUrl":"10.1016/j.yjmcc.2024.11.015","url":null,"abstract":"<div><div>Abnormal valve development is the most common congenital heart malformation. The transcription factor <em>Sox7</em> plays a critical role in the development of vascular and cardiac septation. However, it remains unclear whether <em>Sox7</em> is required for heart valve development. In the present study, Sox7 was strongly expressed in the endocardial and mesenchymal cells of the developing aortic valve in mice and humans, and that endocardial cell specific deletion of Sox7 (Nfatc1 Cre;Sox7^fl/fl) in mice leads to congenital aortic stenosis basing on our echocardiography data and multiple staining results. Mechanistically, Sox7 influences extracellular matrix (ECM) remodeling of the valve through regulating MMP9. Meanwhile, Sox7 also affects other valvular remodeling processes, including apoptosis and proliferation of valvular cells in Sox7 deficiency mice. Similarly, in valvular interstitial cells (VICs), Sox7 overexpression increased the protein levels of cleaved caspase3 and TUNEL-positive VICs, while Ki67-positive VICs decreased. The reverse trend was observed in VICs with Sox7 deficiency. Significant enhancement of Rbm25 transcriptional levels was observed in the Sox7 overexpression group, and the mRNA and protein levels of calcification markers such as Osterix, Osteopontin and Runx2 were reduced. The reverse trend was observed in VICs with Sox7 deficiency. Von Kossa staining and Alizarin Red staining also demonstrated that sever calcification in Nfatc1 Cre;Sox7^fl/fl mice. Moreover, we detected the Sox7 protein expression in human fetal aortic valves in patients with aortic stenosis, in which Sox7 positive mesenchymal cells were decreased. Taken together, these findings identify Sox7 as a potential pathogenic gene responsible for congenital aortic stenosis in human. Our study provides novel strategies for the diagnosis and treatment of congenital valvular malformation.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"199 ","pages":"Pages 81-94"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921975","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":"SIRT6 promotes angiogenesis by enhancing VEGFA secretion via demyristoylation in endothelial cell","authors":"Runyang Feng ,&nbsp;Shuangshuang Chen ,&nbsp;Shichao Duan ,&nbsp;Zhenyang Guo ,&nbsp;Na Wu ,&nbsp;Hangnan Hong ,&nbsp;Zheyan Fang ,&nbsp;Litao Wang ,&nbsp;Yuxin Du ,&nbsp;Lin Wu ,&nbsp;Xin Zhong ,&nbsp;Yiqing Hu ,&nbsp;Zhentao Zhang ,&nbsp;Mukaddas Abdurahman ,&nbsp;Peng Li ,&nbsp;Hua Li ,&nbsp;Junbo Ge","doi":"10.1016/j.yjmcc.2024.12.006","DOIUrl":"10.1016/j.yjmcc.2024.12.006","url":null,"abstract":"<div><div>Angiogenesis plays a pivotal role in ischemic cardiovascular disease, accompanied by epigenetic regulation during this process. Sirtuin 6 (SIRT6) has been implicated in the regulation of DNA repair, transcription and aging, with its deacetylase activity fully studied. However, the role of SIRT6 demyristoylase activity remains less clear, with even less attention given to its myristoylated substrates. In this study, we report that endothelial specific SIRT6 knockout attenuated angiogenesis in mice, while SIRT6 was observed to promote migration and tube formation in endothelial cell. Notably, we further determined that SIRT6 affects the intracellular VEGFA and global myristoylation level under hypoxia. Moreover, ALK14 (myristic acids analogue) treatment and SIRT6 knockdown results in a significant decrease in VEGFA secretion under hypoxia, implying the involvement of SIRT6 demyristoylase activity in angiogenesis. Mechanistically, CLICK IT assay verified that VEGFA is a myristoylated substrate of SIRT6. Further, overexpression of SIRT6 mutants (R65A, G60A and H133Y) results in profound differences in VEGFA secretion, indicating that SIRT6 promotes VEGFA secretion through demyristoylation but not deacetylation. Finally, overexpression of SIRT6 rescued the diminishment of endothelial migration, tube formation and sprouting caused by ALK14 treatment. Overall, our study demonstrates that SIRT6 regulates angiogenesis by demyristoylating VEGFA and increasing VEGFA secretion. Therefore, modulation of SIRT6 demyristoylase activity may represent a therapeutic strategy for ischemic cardiovascular disease.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"199 ","pages":"Pages 104-117"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927126","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":"Extracellular vesicle therapeutics for cardiac repair","authors":"Yilan Hu ,&nbsp;Weihang Zhang ,&nbsp;Shah Rukh Ali ,&nbsp;Koji Takeda ,&nbsp;Torsten Peter Vahl ,&nbsp;Donghui Zhu ,&nbsp;Yi Hong ,&nbsp;Ke Cheng","doi":"10.1016/j.yjmcc.2024.11.005","DOIUrl":"10.1016/j.yjmcc.2024.11.005","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are cell-secreted heterogeneous vesicles that play crucial roles in intercellular communication and disease pathogenesis. Due to their non-tumorigenicity, low immunogenicity, and therapeutic potential, EVs are increasingly used in cardiac repair as cell-free therapy. There exist multiple steps for the design of EV therapies, and each step offers many choices to tune EV properties. Factors such as EV source, cargo, loading methods, routes of administration, surface modification, and biomaterials are comprehensively considered to achieve specific goals. PubMed and Google Scholar were searched in this review, 89 articles related to EV-based cardiac therapy over the past five years (2019 Jan - 2023 Dec) were included, and their key steps in designing EV therapies were counted and analyzed. We aim to provide a comprehensive overview that can serve as a reference guide for researchers to design EV-based cardiac therapies.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"199 ","pages":"Pages 12-32"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739691","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":"Dual inhibition of Mst1 and Mst2 exacerbates cardiac dysfunction during pressure overload stress in mice","authors":"Jin Guan ,&nbsp;Nadezhda Fefelova ,&nbsp;Peiyong Zhai ,&nbsp;Yoshiyuki Ikeda ,&nbsp;Takanobu Yamamoto ,&nbsp;Satvik Mareedu ,&nbsp;Jamie Francisco ,&nbsp;Lai-Hua Xie ,&nbsp;Dae-sik Lim ,&nbsp;Dominic P. Del Re","doi":"10.1016/j.yjmcc.2024.12.009","DOIUrl":"10.1016/j.yjmcc.2024.12.009","url":null,"abstract":"<div><div>Heart failure remains a leading cause of morbidity and mortality worldwide. The evolutionarily conserved Hippo-Yap signaling pathway regulates cardiac responses to stress and progression to heart failure. Mst1 and Mst2 are the core Hippo pathway kinases, yet their role within chronically stressed cardiomyocytes remains largely unknown. Genetic mouse models revealed that the extent of Mst1/2 inhibition elicits opposing effects on stress-induced cardiac dysfunction. Yap-TEAD1 activation, cell cycling, and hallmarks of cardiomyocyte dedifferentiation, which can impair contractile function during sustained stress, were enhanced in Mst1/2 double knockout hearts. These findings implicate a physiological function of Mst1/2 to promote cardiomyocyte maturity in the adult heart.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"199 ","pages":"Pages 133-136"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAPK14/AIFM2 pathway regulates mitophagy-dependent apoptosis to improve atrial fibrillation","authors":"Lu Wang ,&nbsp;Wanyue Sang ,&nbsp;Yi Jian ,&nbsp;Yafan Han ,&nbsp;Feifei Wang ,&nbsp;Subinuer Wubulikasimu ,&nbsp;Li Yang ,&nbsp;Baopeng Tang ,&nbsp;Yaodong Li","doi":"10.1016/j.yjmcc.2024.12.002","DOIUrl":"10.1016/j.yjmcc.2024.12.002","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the role and mechanism of MAPK14/AIFM2 pathway in Ang II-induced atrial fibrillation in rats.</div></div><div><h3>Methods</h3><div>A rat model of AF was established for in vivo experiments and HL-1 cells were treated with Ang II to develop an in vitro model. In addition, HL1 cells overexpressing AIFM2 (oeAIFM2) were constructed. SB203580 was used to inhibit the expression of MAPK14. The role of MAPK14 in Ang II-AF model was investigated by in vivo electrophysiological examination and molecular biology tests. The role of MAPK14 / AIFM2 pathway on AF induced by Ang II was explored in vitro.</div></div><div><h3>Results</h3><div>MAPK14 and AIFM2 were significantly up-regulated in AF induced by Ang II (all <em>P</em> &lt; 0.05). In vivo experiments indicated that inhibition of MAPK14 down-regulated AIFM2, improved atrial electrical conduction, AF inducibility and durations, and alleviated the structural and functional damage of heart and mitochondria (all <em>P</em> &lt; 0.05). Both in vivo and in vitro tests showed that the MAPK14/AIFM2 pathway prevented Ang II-induced AF via regulating mitophagy-dependent apoptosis.</div></div><div><h3>Conclusions</h3><div>Inhibition of the MAPK14/AIFM2 pathway improved Ang II-induced AF by inhibiting mitophagy-dependent apoptosis.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"199 ","pages":"Pages 1-11"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807252","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":"Prevalence of rare missense TTN variants in a cohort of patients with cardiomyopathy","authors":"Irene Bottillo ,&nbsp;Maria Pia Ciccone ,&nbsp;Monia Magliozzi ,&nbsp;Kalliopi Pilichou ,&nbsp;Giorgia Girotto ,&nbsp;Francesca Girolami ,&nbsp;Massimiliano Cecconi ,&nbsp;Valeria D'Argenio ,&nbsp;Valeria Novelli ,&nbsp;Alessandra Coiana ,&nbsp;Daniela Formicola ,&nbsp;Emanuele Micaglio ,&nbsp;Giada Tortora ,&nbsp;Francesca Gualandi ,&nbsp;Simona Petrucci ,&nbsp;Italian Cardiogenetics Study Group,&nbsp;Marco Castori ,&nbsp;Nicoletta Resta ,&nbsp;Anna Rita Vestri ,&nbsp;Maria Iascone ,&nbsp;Paola Grammatico","doi":"10.1016/j.yjmcc.2024.12.004","DOIUrl":"10.1016/j.yjmcc.2024.12.004","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"199 ","pages":"Pages 46-50"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824257","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":"KLF2-dependent transcriptional regulation safeguards the heart against pathological hypertrophy","authors":"Yongqi Wu ,&nbsp;Yujuan Song ,&nbsp;Nan Xie ,&nbsp;Wanqing Zhao ,&nbsp;Jian Lv ,&nbsp;Tingting Zhang ,&nbsp;Yang Zhang ,&nbsp;Hongyin Chen ,&nbsp;Weiyun Sun ,&nbsp;Zhenyu Luo ,&nbsp;Xinhui Cheng ,&nbsp;Tao Jiang ,&nbsp;Zhihua Wang ,&nbsp;Xiaoling Chen ,&nbsp;Yu Hu ,&nbsp;Yu Fang ,&nbsp;Rui Bai ,&nbsp;Xujie Liu ,&nbsp;Xia He ,&nbsp;Zongna Ren ,&nbsp;Li Wang","doi":"10.1016/j.yjmcc.2024.12.010","DOIUrl":"10.1016/j.yjmcc.2024.12.010","url":null,"abstract":"<div><h3>Background</h3><div>Our previous single-cell RNA sequencing study in the adult human heart revealed that cardiomyocytes from both the atrium and ventricle display high activities of Krüppel-like factor 2 (KLF2) regulons. However, the role of the transcription factor KLF2 in cardiomyocyte biology remains largely unexplored.</div></div><div><h3>Methods and results</h3><div>We employed transverse aortic constriction surgery in male C57BL/6 J mice to develop an <em>in vivo</em> model of cardiac hypertrophy, and generated different <em>in vitro</em> cardiac hypertrophy models in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes. Our results demonstrated a significant reduction in KLF2 expression during the progression of cardiac hypertrophy. <em>In vitro</em>, <em>Klf2</em> deficiency exacerbates cardiac hypertrophy and enhances hypertrophic reprogramming, while KLF2 overexpression attenuates cardiac hypertrophy and reverses hypertrophic transcriptome reprogramming. Mechanistically, combined RNA-seq and cleavage under targets &amp; tagmentation (CUT&amp;Tag) analysis revealed that KLF2 exerts its protective effects by directly regulating a set of genes associated with cardiac hypertrophy. <em>In vivo</em>, KLF2 overexpression specifically in cardiomyocytes effectively prevents TAC-induced cardiac hypertrophy in mice. Additionally, we found that simvastatin elevates KLF2 expression in cardiomyocytes, which subsequently alleviates cardiomyocyte hypertrophy.</div></div><div><h3>Conclusions</h3><div>This study provides the first evidence that transcription factor KLF2 serves as a negative regulator of cardiac hypertrophy. Our findings highlight the therapeutic potential of enhancing KLF2 expression, particularly through simvastatin administration, as a promising strategy in the treatment of cardiac hypertrophy.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"199 ","pages":"Pages 62-77"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903296","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}