Journal of molecular and cellular cardiology plus最新文献

{"title":"Starting off strong: Rigor and reproducibility in the early career","authors":"Ronald J. Vagnozzi","doi":"10.1016/j.jmccpl.2022.100022","DOIUrl":"10.1016/j.jmccpl.2022.100022","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976122000162/pdfft?md5=8e1846d23b05b6cb46fdd4abc65a2654&pid=1-s2.0-S2772976122000162-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46655933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A gradient of force generation at rest differentiates cardiomyopathy outcomes with variants of actin located at the same residue","authors":"Michael R. Jones,&nbsp;Chau Tran ,&nbsp;Jaskerat Singh ,&nbsp;John F. Dawson","doi":"10.1016/j.jmccpl.2022.100023","DOIUrl":"10.1016/j.jmccpl.2022.100023","url":null,"abstract":"<div><p>The calcium sensitivity hypothesis helps explain the development of different forms of cardiomyopathy: increased sensitivity to calcium in cardiac sarcomeres leads to hypertrophic cardiomyopathy (HCM) and decreased sensitivity results in dilated cardiomyopathy (DCM). This hypothesis has driven the development of next generation drugs targeting sarcomere proteins to correct the amount of force generated as a result of changes in calcium sensitivity (<em>e.g.</em> mavacamten decreases cardiac myosin activity to treat HCM). Characterization of variants of cardiac actin (ACTC) found in patients with HCM or DCM has generally supported the calcium sensitivity hypothesis. Of interest are two different substitution mutations at R312 on ACTC: R312H leads to DCM, while R312C was found in patients with HCM. To determine how changes in the same codon on the same gene lead to different disease phenotypes, we characterized recombinant R312H- and R312C-ACTC variant proteins. Both variants exhibited the same change in calcium sensitivity, suggesting that a factor other than calcium sensitivity is responsible for disease differentiation. We observed a gradient of increased residual myosin activity with R312-ACTC variant proteins under relaxing conditions which may trigger different disease development. Our findings suggest that factors other than calcium sensitivity may contribute to cardiomyopathy development and should be considered when planning treatments.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976122000174/pdfft?md5=b049a1ef4f9c14330dca36acfb90cff4&pid=1-s2.0-S2772976122000174-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46871693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How low can you go – Insight into the level of mutated protein required to cause pathogenic effects in hypertrophic cardiomyopathy","authors":"Katja Gehmlich","doi":"10.1016/j.jmccpl.2022.100009","DOIUrl":"10.1016/j.jmccpl.2022.100009","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976122000034/pdfft?md5=d0c9ffc67f13365ab17620ced2391b4c&pid=1-s2.0-S2772976122000034-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44196077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the DBA/2J mouse as a potential background strain for genetic models of cardiomyopathy","authors":"Cora C. Hart,&nbsp;Young il Lee,&nbsp;David W. Hammers ,&nbsp;H. Lee Sweeney","doi":"10.1016/j.jmccpl.2022.100012","DOIUrl":"10.1016/j.jmccpl.2022.100012","url":null,"abstract":"<div><p>The potential use of the D2.<em>mdx</em> mouse (the <em>mdx</em> mutation on the DBA/2J genetic background) as a preclinical model of the cardiac aspects of Duchenne muscular dystrophy (DMD) has been criticized based on speculation that the DBA/2J genetic background displays an inherent hypertrophic cardiomyopathy (HCM) phenotype. Accordingly, the goal of the current study was to further examine the cardiac status of this mouse strain over a 12-month period to determine if observable signs of HCM develop, including histopathology and pathological enlargement of the myocardium. Previous reports have documented heightened TGFβ signaling in the DBA2/J striated muscles, as compared to the C57 background, which, as expected, is manifested as increased cardiomyocyte size, wall thickness, and heart mass as compared to the C57 background. While normalized heart mass is larger in the DBA/2J mice, compared to age-matched C57/BL10 mice, both strains similarly increase in size from 4 to 12 months of age. We also report that DBA/2J mice contain equivalent amounts of left ventricular collagen as healthy canine and human samples. In a longitudinal echocardiography study, neither sedentary nor exercised DBA/2J mice demonstrated left ventricular wall thickening or cardiac functional deficits. In summary, we find no evidence of HCM, nor any other cardiac pathology, and thus propose that it is an appropriate background strain for genetic modeling of cardiac diseases, including the cardiomyopathy associated with DMD.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/79/b4/nihms-1895617.PMC10195103.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low expression of the K280N TNNT2 mutation is sufficient to increase basal myofilament activation in human hypertrophy cardiomyopathy","authors":"Vasco Sequeira ,&nbsp;Lili Wang ,&nbsp;Paul J.M. Wijnker ,&nbsp;Kyungsoo Kim ,&nbsp;Jose R. Pinto ,&nbsp;Cris dos Remedios ,&nbsp;Charles Redwood ,&nbsp;Bjorn C. Knollmann ,&nbsp;Jolanda van der Velden","doi":"10.1016/j.jmccpl.2022.100007","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2022.100007","url":null,"abstract":"<div><h3>Background</h3><p>Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder with patients typically showing heterozygous inheritance of a pathogenic variant in a gene encoding a contractile protein. Here, we study the contractile effects of a rare homozygous mutation using explanted tissue and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to gain insight into how the balance between mutant and WT protein expression affects cardiomyocyte function.</p></div><div><h3>Methods</h3><p>Force measurements were performed in cardiomyocytes isolated from a HCM patient carrying a homozygous troponin T mutation (cTnT-K280N) and healthy donors. To discriminate between mutation-mediated and phosphorylation-related effects on Ca²⁺-sensitivity, cardiomyocytes were treated with alkaline phosphatase (AP) or protein kinase A (PKA). Troponin exchange experiments characterized the relation between mutant levels and myofilament function. To define mutation-mediated effects on Ca²⁺-dynamics we used CRISPR/Cas9 to generate hiPSC-CMs harbouring heterozygous and homozygous TnT-K280N mutations. Ca²⁺-transient and cell shortening experiments compared these lines against isogenic controls.</p></div><div><h3>Results</h3><p>Myofilament Ca²⁺-sensitivity was higher in homozygous cTnT-K280N cardiomyocytes and was not corrected by AP- and PKA-treatment. In cTnT-K280N cells exchanged with cTnT-WT, a low level (14%) of cTnT-K280N mutation elevated Ca²⁺-sensitivity. Similarly, exchange of donor cells with 45 ± 2% cTnT-K280N increased Ca²⁺-sensitivity and was not corrected by PKA. cTnT-K280N hiPSC-CMs show elevated diastolic Ca²⁺ and increases in cell shortening. Impaired cardiomyocyte relaxation was only evident in homozygous cTnT-K280N hiPSC-CMs.</p></div><div><h3>Conclusions</h3><p>The cTnT-K280N mutation increases myofilament Ca²⁺-sensitivity, elevates diastolic Ca²⁺, enhances contractility and impairs cellular relaxation. A low level (14%) of the cTnT-K280N sensitizes myofilaments to Ca²⁺, a universal finding of human HCM.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976122000010/pdfft?md5=02353d529c9a9baa030202105ba7309c&pid=1-s2.0-S2772976122000010-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91685285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(Epi)transcriptomics in cardiovascular and neurological complications of COVID-19","authors":"Amela Jusic ,&nbsp;Konstantinos Stellos ,&nbsp;Lino Ferreira ,&nbsp;Andrew H. Baker ,&nbsp;Yvan Devaux","doi":"10.1016/j.jmccpl.2022.100013","DOIUrl":"10.1016/j.jmccpl.2022.100013","url":null,"abstract":"<div><p>Although systemic inflammation and pulmonary complications increase the mortality rate in COVID-19, a broad spectrum of cardiovascular and neurological complications can also contribute to significant morbidity and mortality.</p><p>The molecular mechanisms underlying cardiovascular and neurological complications during and after SARS-CoV-2 infection are incompletely understood. Recently reported perturbations of the epitranscriptome of COVID-19 patients indicate that mechanisms including those derived from RNA modifications and non-coding RNAs may play a contributing role in the pathogenesis of COVID-19.</p><p>In this review paper, we gathered recently published studies investigating (epi)transcriptomic fluctuations upon SARS-CoV-2 infection, focusing on the brain-heart axis since neurological and cardiovascular events and their sequelae are of utmost prevalence and importance in this disease.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10712162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomic analyses reveal enriched glycolytic processes in β-myosin heavy chain-expressed cardiomyocytes in early cardiac hypertrophy","authors":"Hsiao-hui Yeh ,&nbsp;Yao-Ming Chang ,&nbsp;Yu-Wang Chang ,&nbsp;Mei-Yeh Jade Lu ,&nbsp;Yi-Hua Chen ,&nbsp;Chia-Che Lee ,&nbsp;Chien-Chang Chen","doi":"10.1016/j.jmccpl.2022.100011","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2022.100011","url":null,"abstract":"<div><h3>Background</h3><p>Cardiac pressure overload induces cardiac hypertrophy and eventually leads to heart failure. One distinct feature of pathological cardiac hypertrophy is fetal-gene re-expression, but not every cardiomyocyte exhibits fetal gene re-expression in the diseased heart. Adult cardiomyocytes are terminally differentiated cells, so we do not know how the heterogeneity is determined and whether the differential fetal-gene reprogramming indicates a different degree of remodeling among cardiomyocytes. We hypothesized that fetal gene-expressed cardiomyocytes show more pathological features in the pressure-overloaded heart.</p></div><div><h3>Results</h3><p>We induced pressure overload in mice by transverse aortic constriction (TAC) and observed a cardiomyocyte population with expression of β-myosin heavy chain (βMHC, a fetal gene encoded by <em>Myh7</em>) after TAC for 3 days. On transcriptomic and proteomic analyses, βMHC-expressed cardiomyocytes of 3-day TAC hearts were enriched in genes in cardiomyopathy-associated pathways and glycolytic processes. Moreover, results of immunoblotting and enzyme activity assay suggested higher glycolytic activity in βMHC-expressed than non-expressed cardiomyocytes. When we inhibited the glycolytic flux by 2-deoxy-<span>d</span>-glucose, a widely used glycolysis inhibitor, the number of βMHC-expressed cardiomyocytes was reduced, and the level of TEA domain family member 1 (TEAD1), a transcriptional enhancer, was decreased. Also, our spatial transcriptomic results demonstrated that naïve and 3-day TAC hearts had fetal-gene–rich tissue domains that were enriched in pathways in extracellular matrix organization and tissue remodeling. As well, gene levels of glycolytic enzymes were higher in <em>Myh7</em>-positive than <em>Myh7</em>-negative domains.</p></div><div><h3>Conclusions</h3><p>Our data suggest that βMHC-expressed cardiomyocytes progress to pathological remodeling in the early stages of cardiac hypertrophy. In addition, the diverse glycolytic activity among cardiomyocytes might play a role in regulating gene expression via TEAD1 signaling.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976122000058/pdfft?md5=33ea72a7a407ecf57335d0fa20f5f476&pid=1-s2.0-S2772976122000058-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91685284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serial measurements of protein and microRNA biomarkers to specify myocardial infarction subtypes","authors":"Christian Schulte ,&nbsp;Bhawana Singh ,&nbsp;Konstantinos Theofilatos ,&nbsp;Nils A. Sörensen ,&nbsp;Jonas Lehmacher ,&nbsp;Tau Hartikainen ,&nbsp;Paul M. Haller ,&nbsp;Dirk Westermann ,&nbsp;Tanja Zeller ,&nbsp;Stefan Blankenberg ,&nbsp;Johannes T. Neumann ,&nbsp;Manuel Mayr","doi":"10.1016/j.jmccpl.2022.100014","DOIUrl":"10.1016/j.jmccpl.2022.100014","url":null,"abstract":"<div><h3>Background</h3><p>While cardiac-specific troponin (cTn) allows for rapid diagnosis of acute type 1 myocardial infarction (T1MI), its performance to differentiate acute myocardial injury (AI) or type 2 myocardial infarction (T2MI) is limited. The objective was to combine biomarkers to improve discrimination of different myocardial infarction (MI) aetiologies.</p></div><div><h3>Methods</h3><p>We determined levels of cardiac troponin T and I (cTnT, cTnI), cardiac myosin-binding protein C (cMyBP-C), NT-proBNP and ten miRNAs, known to be associated with cardiac pathology in a total of <em>n</em> = 495 serial plasma samples at three time points (on admission, after 1 h and 3 h) from 57 NSTEMI (non-ST-elevation myocardial infarction), 18 AI, and 31 STEMI patients, as defined by fourth universal definition of MI (UDMI4) and 59 control individuals. We then applied linear mixed effects model to compare the kinetics of all molecules in these MI sub-types.</p></div><div><h3>Results</h3><p>Established (cTnT, cTnI) and novel (cMyBP-C) cardiac necrosis markers failed in differentiating T1MI vs T2MI at early time points. All cardiac necrosis markers were higher in T1MI than in T2MI at 3 h after admission. Muscle-enriched miRNAs (miR-1 and miR-133a) were correlated with cardiac necrosis protein markers and did not offer better discrimination. Established cardiac strain marker NT-proBNP differentiated AI and T1MI at all time points but failed to discriminate T2MI from T1MI. However, the combination of NT-proBNP and cTnT along with age returned an overall AUC of 0.76 [95 % CI 0.67–0.84] for differentiating T1MI, T2MI and AI.</p></div><div><h3>Conclusions</h3><p>Rather than using single biomarkers of myocardial necrosis, a combination of clinical biomarkers for cardiac necrosis (troponin) and cardiac strain (NT-proBNP) might aid in differentiating T1MI, T2MI and AI.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/15/8c/main.PMC9514835.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40387001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introducing JMCC Plus, ISHR's new open access journal","authors":"Rong Tian ,&nbsp;Davor Pavlovic","doi":"10.1016/j.jmccpl.2022.100008","DOIUrl":"10.1016/j.jmccpl.2022.100008","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976122000022/pdfft?md5=a2a3c3780db08ac76e10f42610847359&pid=1-s2.0-S2772976122000022-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47077647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wnt signaling pathway in the development of atherosclerosis: Sclerostin as a new surrogate marker of global vascular calcification?","authors":"P. Kocełak, M. Puzianowska-Kuźnicka, M. Olszanecka-Glinianowicz, J. Chudek","doi":"10.1016/j.jmccpl.2022.100010","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2022.100010","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43334834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}