Journal of molecular and cellular cardiology最新文献

{"title":"Hyaluronan provokes inflammation but suppresses phagocytotic function in macrophages","authors":"Timothy N. Audam ,&nbsp;Caitlin M. Howard ,&nbsp;Danielle T. Little ,&nbsp;Lauren F. Garrett ,&nbsp;Yi Wei Zheng ,&nbsp;Zhen Gu ,&nbsp;Kenneth R. Brittian ,&nbsp;Raéden Gray ,&nbsp;Julia Chariker ,&nbsp;Richa A. Singhal ,&nbsp;Marcin Wysoczynski ,&nbsp;Steven P. Jones","doi":"10.1016/j.yjmcc.2024.11.009","DOIUrl":"10.1016/j.yjmcc.2024.11.009","url":null,"abstract":"<div><h3>Background</h3><div>The extracellular matrix (ECM) provides structural and functional support for the myocardium, but myocardial infarction (MI) changes the composition of the ECM. One of the chief components of the ECM, hyaluronan (HA), accumulates after MI; however, specific biological actions of HA—particularly at the level of infiltrating immune cells and implications of such interactions on ventricular remodeling—have not been explored.</div></div><div><h3>Goal</h3><div>Because acute accumulation of HA coincides with macrophage infiltration after MI, we assessed the impact of HA on macrophage function.</div></div><div><h3>Results</h3><div>Compared to SHAM hearts, HA levels were elevated in both the infarct and remote regions of infarcted hearts. Because acute accumulation of HA coincides with macrophage infiltration after MI, we explored the implication of HA accumulation on various endpoints of macrophage function, including macrophage activation, phagocytosis, and efferocytosis. Our data suggests that exposing macrophages to HA^HMW pushes macrophages toward a more pro-inflammatory phenotype as indicated by increased secretion of pro-inflammatory signals such as IL-2, IL-17, and IP-10<em>.</em> Our data also suggests that in the presence of HA, both macrophage efferocytosis and Fc-receptor dependent phagocytosis are suppressed. These results are unique to treatment with HA^HMW, as similar results were not observed when cells were treated with HA^LMW. Using macrophages from <em>Cd44</em>^{<em>−/−</em>} mice, we determined that while the impact of HA^HMW on cytokine secretion does seem to be dependent in part on <em>Cd44</em> expression, the impact on macrophage phagocytosis is independent. Since macrophage efferocytosis of dying cardiomyocytes and cellular debris is critical following MI, we believe that this response will prolong the resolution of inflammation and lead to maladaptive remodeling.</div></div><div><h3>Conclusion</h3><div>HA accumulates post-MI and may promote a pro-inflammatory phenotype in macrophages. Future studies will explore the extent to which post infarct HA accumulation regulates cardiac macrophage dynamics and function <em>in vivo</em>.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"198 ","pages":"Pages 24-35"},"PeriodicalIF":4.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746664","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":"Transcriptomic analysis of nicotine on the cardiovascular system using a diverse population of human induced pluripotent stem cell-derived endothelial cells","authors":"Nerea Jimenez-Tellez ,&nbsp;Damon Williams ,&nbsp;Yu Liu ,&nbsp;Mingqiang Wang ,&nbsp;Mark Chandy ,&nbsp;Joseph C. Wu","doi":"10.1016/j.yjmcc.2024.11.001","DOIUrl":"10.1016/j.yjmcc.2024.11.001","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"198 ","pages":"Pages 21-23"},"PeriodicalIF":4.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721393","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":"Leukocyte-lymphatic intersections during cardiac inflammation","authors":"Kristofor Glinton ,&nbsp;Abhishek V. Thakkar ,&nbsp;Rebecca Jones ,&nbsp;Hiroyasu Inui ,&nbsp;Zhi-Dong Ge ,&nbsp;Edward B. Thorp","doi":"10.1016/j.yjmcc.2024.11.006","DOIUrl":"10.1016/j.yjmcc.2024.11.006","url":null,"abstract":"<div><div>Advances in genetic, pharmacologic, and sequencing technology have led to new insight into the role of lymphatics in health and disease. This includes fundamental aspects of the crosstalk between immune cells with cardiac lymphatics. At the interface between leukocytes and lymphatic endothelial cells, myeloid populations are sources of lymphatic growth factors during inflammation. Lymphatic endothelial cells also secrete signals that activate leukocytes, including to antigen presenting cells. Taken together, a view of the lymphatic vasculature as a supplemental cardiac immune hub is emerging. Herein, we discuss reciprocal cell and molecular crosstalk between leukocytes and lymphatics in the myocardium, with implications for health and cardiac inflammation.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"198 ","pages":"Pages 13-20"},"PeriodicalIF":4.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721392","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":"PERM1 regulates mitochondrial energetics through O-GlcNAcylation in the heart","authors":"Karthi Sreedevi ,&nbsp;Amina James ,&nbsp;Sara Do ,&nbsp;Shreya Yedla ,&nbsp;Sumaita Arowa ,&nbsp;Shin-ichi Oka ,&nbsp;Adam R. Wende ,&nbsp;Alexey V. Zaitsev ,&nbsp;Junco S. Warren","doi":"10.1016/j.yjmcc.2024.11.002","DOIUrl":"10.1016/j.yjmcc.2024.11.002","url":null,"abstract":"<div><div>PERM1 was initially identified as a new downstream target of PGC-1α and ERRs that regulates mitochondrial bioenergetics in skeletal muscle. Subsequently, we and other groups demonstrated that PERM1 is also a positive regulator of mitochondrial bioenergetics in the heart. However, the exact mechanisms of regulatory functions of PERM1 remain poorly understood. O-GlcNAcylation is a post-translational modification of proteins that are regulated by two enzymes: O-GlcNAc transferase (OGT) that adds O-GlcNAc to proteins; O-GlcNAcase (OGA) that removes O-GlcNAc from proteins. O-GlcNAcylation is a powerful signaling mechanism mediating cellular responses to stressors and nutrient availability, which, among other targets, may influence cardiac metabolism. We hypothesized that PERM1 regulates mitochondrial energetics in cardiomyocytes through modulation of O-GlcNAcylation. We found that overexpression of PERM1 decreased the total levels of O-GlcNAcylated proteins, concomitant with decreased OGT and increased OGA expression levels. Luciferase gene reporter assay showed that PERM1 significantly decreases the promoter activity of <em>Ogt</em> without changing the promoter activity of <em>Oga</em>. The downregulation of OGT by PERM1 overexpression was mediated through its interaction with E2F1, a known transcription repressor of <em>Ogt</em>. A deliberate increase of O-GlcNAcylation through <em>Oga</em> silencing in cardiomyocytes decreased the basal and maximal mitochondrial respiration and ATP production rates, all of which were completely restored by PERM1 overexpression. Furthermore, excessive O-GlcNAcylation caused by the loss of PERM1 led to the increase of O-GlcNAcylated PGC-1α, a master regulator of mitochondrial bioenergetics, concurrent with the dissociation of PGC-1α from PPARα, a well-known transcription factor that regulates fatty acid β-oxidation. We conclude that PERM1 positively regulates mitochondrial energetics, in part, via suppressing O-GlcNAcylation in cardiac myocytes.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"198 ","pages":"Pages 1-12"},"PeriodicalIF":4.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701080","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":"Retraction notice to “The novel antibody fusion protein rhNRG1-HER3i promotes heart regeneration by enhancing NRG1-ERBB4 signaling pathway” [Journal of Molecular and Cellular Cardiology 187 (2023) 26–37]","authors":"Xuemei Wang ,&nbsp;Hao Wu ,&nbsp;Luxun Tang ,&nbsp;Wenbin Fu ,&nbsp;Yanji He ,&nbsp;Chunyu Zeng ,&nbsp;Wei Eric Wang","doi":"10.1016/j.yjmcc.2024.09.009","DOIUrl":"10.1016/j.yjmcc.2024.09.009","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Page 151"},"PeriodicalIF":4.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648336","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":"Exercise training attenuates cardiac dysfunction induced by excessive sympathetic activation through an AMPK-KLF4-FMO2 axis","authors":"Shiyu Fan ,&nbsp;Mingming Zhao ,&nbsp;Kang Wang ,&nbsp;Yawen Deng ,&nbsp;Xiaoyue Yu ,&nbsp;Ketao Ma ,&nbsp;Youyi Zhang ,&nbsp;Han Xiao","doi":"10.1016/j.yjmcc.2024.10.015","DOIUrl":"10.1016/j.yjmcc.2024.10.015","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide and are associated with an overactivated sympathetic system. Although exercise training has shown promise in mitigating sympathetic stress-induced cardiac remodeling, the precise mechanisms remain elusive. Here, we demonstrate that exercise significantly upregulates cardiac flavin-containing monooxygenase 2 (FMO2) expression. Notably, we find that exercise training effectively counteracts sympathetic overactivation-induced cardiac dysfunction and fibrosis by enhancing FMO2 expression via adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) activation. Functional investigations employing FMO2 knockdown with adeno-associated virus 9 (AAV9) underscore the necessity for FMO2 expression to protect the heart during exercise in vivo. Furthermore, we identify the krüppel-like factor 4 (KLF4) as a transcriptional mediator of FMO2 that is crucial for the mechanism through which AMPK activation protects against sympathetic overactivation-induced cardiac dysfunction and fibrosis. Taken together, our study reveals a cardioprotective mechanism for exercise training through an AMPK-KLF4-FMO2 signaling pathway that underscores how exercise alleviates cardiac dysfunction induced by excessive sympathetic activation.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 136-149"},"PeriodicalIF":4.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566354","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":"Different effects of cardiomyocyte contractile activity on transverse and axial tubular system luminal content dynamics","authors":"J. Greiner ,&nbsp;M. Dente ,&nbsp;S. Orós-Rodrigo ,&nbsp;B.A. Cameron ,&nbsp;J. Madl ,&nbsp;W. Kaltenbacher ,&nbsp;T. Kok ,&nbsp;C.M. Zgierski-Johnston ,&nbsp;R. Peyronnet ,&nbsp;P. Kohl ,&nbsp;L. Sacconi ,&nbsp;E.A. Rog-Zielinska","doi":"10.1016/j.yjmcc.2024.10.014","DOIUrl":"10.1016/j.yjmcc.2024.10.014","url":null,"abstract":"<div><h3>Background</h3><div>Efficient excitation-contraction coupling of mammalian ventricular cardiomyocytes depends on the transverse-axial tubular system (TATS), a network of surface membrane invaginations. TATS enables tight coupling of sarcolemmal and sarcoplasmic reticulum membranes, which is essential for rapid Ca²⁺-induced Ca²⁺ release, and uniform contraction upon electrical stimulation. The majority of TATS in healthy ventricular cardiomyocytes is composed of transverse tubules (TT, ∼90 % of TATS in rabbit). The remainder consists of mostly axial tubules (AT), which are less abundant and less well studied. In disease, however, the relative abundance of TT and AT changes. The mechanisms and relevance of this change are not known, and understanding them requires a more targeted effort to study the dynamics of AT structure and function.</div><div>While TATS content is continuous with the interstitial space, it is contained within a domain of restricted diffusion. We have previously shown that TT are cyclically squeezed during stretch and contraction. This can contribute to TT content mixing and accelerates luminal content exchange with the environment. Here, we explore the effects of cardiomyocyte stretch and contraction on AT.</div></div><div><h3>Methods</h3><div>TATS structure and diffusion dynamics were studied using 3D electron tomography of rabbit left ventricular cardiomyocytes, preserved at rest or during contraction, and ventricular tissue preserved at rest or during stretch, as well as live-cell TATS content exchange measurements.</div></div><div><h3>Results</h3><div>We show (i) that cardiomyocyte contraction is associated with an increase in the apparent speed of diffusion of TT content that scales with beating rate and degree of cell shortening. In contrast, (ii) AT develop membrane folds and constrictions during contraction, (iii) with no effect of contraction on luminal exchange dynamics, while (iv) cardiomyocyte stretch is associated with AT straightening and AT and TT ‘squeezing’ that (v) supports an acceleration of the apparent speed of diffusion in AT and TT. Finally, (vi) we present a simple computational model outlining the potential relevance of AT in healthy and diseased cells.</div></div><div><h3>Conclusions</h3><div>Our results indicate that TT and AT are differently affected by the cardiac contractile cycle, and suggest that AT may play a role in ensuring TATS network content homogeneity in diseased cardiomyocytes. Further research is needed to explore the interplay of structural and functional remodelling of different TATS components in failing myocardium.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 125-135"},"PeriodicalIF":4.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568957","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":"Macrophages in the infarcted heart acquire a fibrogenic phenotype, expressing matricellular proteins, but do not undergo fibroblast conversion","authors":"Ruoshui Li ,&nbsp;Anis Hanna ,&nbsp;Shuaibo Huang ,&nbsp;Silvia C. Hernandez ,&nbsp;Izabela Tuleta ,&nbsp;Akihiko Kubota ,&nbsp;Claudio Humeres ,&nbsp;Bijun Chen ,&nbsp;Yang Liu ,&nbsp;Deyou Zheng ,&nbsp;Nikolaos G. Frangogiannis","doi":"10.1016/j.yjmcc.2024.07.010","DOIUrl":"10.1016/j.yjmcc.2024.07.010","url":null,"abstract":"<div><div>Although some studies have suggested that macrophages may secrete structural collagens, and convert to fibroblast-like cells, macrophage to fibroblast transdifferentiation in infarcted and remodeling hearts remains controversial. Our study uses linage tracing approaches and single cell transcriptomics to examine whether macrophages undergo fibroblast conversion, and to characterize the extracellular matrix expression profile of myeloid cells in myocardial infarction. To examine whether infarct macrophages undergo fibroblast conversion, we identified macrophage-derived progeny using the inducible CX3CR1^CreER mice crossed with the PDGFRα^EGFP reporter line for reliable fibroblast identification. The abundant fibroblasts that infiltrated the infarcted myocardium after 7 and 28 days of coronary occlusion were not derived from CX3CR1+ macrophages. Infarct macrophages retained myeloid cell characteristics and did not undergo conversion to myofibroblasts, endothelial or vascular mural cells. Single cell RNA-seq of CSF1R+ myeloid cells harvested from control and infarcted hearts showed no significant expression of fibroblast identity genes by myeloid cell clusters. Moreover, infarct macrophages did not express significant levels of genes encoding structural collagens. However, infarct macrophage and monocyte clusters were the predominant source of the fibrogenic growth factors <em>Tgfb1</em> and <em>Pdgfb,</em> and of the matricellular proteins <em>Spp1</em>/Osteopontin, <em>Thbs1</em>/Thrombospondin-1, <em>Emilin2</em>, and <em>Fn1</em>/fibronectin, while expressing significant amounts of several other matrix genes, including <em>Vcan</em>/versican, <em>Ecm1</em> and <em>Sparc</em>. ScRNA-seq data suggested similar patterns of matrix gene expression in human myocardial infarction. In conclusion, infarct macrophages do not undergo fibroblast or myofibroblast conversion and do not exhibit upregulation of structural collagens but may contribute to fibrotic remodeling by producing several fibrogenic matricellular proteins.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"196 ","pages":"Pages 152-167"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875092","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":"Cardiac macrophages and fibroblasts: A synergistic partnership without cellular transition","authors":"Daniel A. Kasprovic ,&nbsp;Robert M. Jaggers ,&nbsp;Michael Tranter ,&nbsp;Onur Kanisicak","doi":"10.1016/j.yjmcc.2024.09.008","DOIUrl":"10.1016/j.yjmcc.2024.09.008","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"196 ","pages":"Pages 168-170"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289359","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":"Integrated proteomics and transcriptomics analysis reveals insights into differences in premature mortality associated with disparate pathogenic RBM20 variants","authors":"Zachery R. Gregorich ,&nbsp;Eli J. Larson ,&nbsp;Yanghai Zhang ,&nbsp;Camila U. Braz ,&nbsp;Chunling Liu ,&nbsp;Ying Ge ,&nbsp;Wei Guo","doi":"10.1016/j.yjmcc.2024.10.013","DOIUrl":"10.1016/j.yjmcc.2024.10.013","url":null,"abstract":"<div><div>Variants in RNA binding motif protein 20 (RBM20) are causative in a severe form of dilated cardiomyopathy referred to as RBM20 cardiomyopathy, yet the mechanisms are unclear. Moreover, the reason(s) for phenotypic heterogeneity in carriers with different pathogenic variants are similarly opaque. To gain insight, we carried out multi-omics analysis, including the first analysis of gene expression changes at the protein level, of mice carrying two different pathogenic variants in the RBM20 nuclear localization signal (NLS). Direct comparison of the phenotypes confirmed greater premature morality in S639G variant carrying mice compared to mice with the S637A variant despite similar cardiac remodeling and dysfunction. Analysis of differentially spliced genes uncovered alterations in the splicing of both RBM20 target genes and non-target genes, including several genes previously implicated in arrhythmia. Global proteomics analysis found that a greater number of proteins were differentially expressed in the hearts of <em>Rbm20</em>^S639G mice relative to WT than in <em>Rbm20</em>^S637A versus WT. Gene ontology analysis suggested greater mitochondrial dysfunction in <em>Rbm20</em>^S639G mice, although direct comparison of protein expression in the hearts of <em>Rbm20</em>^S639G versus <em>Rbm20</em>^S637A mice failed to identify any significant differences. Similarly, few differences were found by direct comparison of gene expression at the transcript level in <em>Rbm20</em>^S639G and <em>Rbm20</em>^S637A despite greater coverage. Our data provide a comprehensive overview of gene splicing and expression differences associated with pathogenic variants in RBM20, as well as insights into the molecular underpinnings of phenotypic heterogeneity associated with different dilated cardiomyopathy-associated variants.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"197 ","pages":"Pages 78-89"},"PeriodicalIF":4.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553014","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}