Journal of molecular and cellular cardiology plus最新文献

{"title":"Distinct phenotypes induced by acute hypoxia and TGF-β1 in human adult cardiac fibroblasts","authors":"Natalie N. Khalil ,&nbsp;Megan L. Rexius-Hall ,&nbsp;Sean Escopete ,&nbsp;Sarah J. Parker ,&nbsp;Megan L. McCain","doi":"10.1016/j.jmccpl.2024.100080","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2024.100080","url":null,"abstract":"<div><p>Myocardial infarction (MI) causes hypoxic injury to downstream myocardial tissue, which initiates a wound healing response that replaces injured myocardial tissue with a scar. Wound healing is a complex process that consists of multiple phases, in which many different stimuli induce cardiac fibroblasts to differentiate into myofibroblasts and deposit new matrix. While this process is necessary to replace necrotic tissue, excessive and unresolved fibrosis is common post-MI and correlated with heart failure. Therefore, defining how cardiac fibroblast phenotypes are distinctly regulated by stimuli that are prevalent in the post-MI microenvironment, such as hypoxia and transforming growth factor-beta (TGF-β), is essential for understanding and ultimately mitigating pathological fibrosis. In this study, we acutely treated primary human adult cardiac fibroblasts with TGF-β1 or hypoxia and then characterized their phenotype through immunofluorescence, quantitative RT-PCR, and proteomic analysis. We found that fibroblasts responded to low oxygen with increased localization of hypoxia inducible factor 1 (HIF-1) to the nuclei after 4 h, which was followed by increased gene expression of vascular endothelial growth factor A (VEGFA), a known target of HIF-1, by 24 h. Both TGF-β1 and hypoxia inhibited proliferation after 24 h. TGF-β1 treatment also upregulated various fibrotic pathways. In contrast, hypoxia caused a reduction in several protein synthesis pathways, including collagen biosynthesis. Collectively, these data suggest that TGF-β1, but not acute hypoxia, robustly induces the differentiation of human cardiac fibroblasts into myofibroblasts. Discerning the overlapping and distinctive outcomes of TGF-β1 and hypoxia treatment is important for elucidating their roles in fibrotic remodeling post-MI and provides insight into potential therapeutic targets.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976124000205/pdfft?md5=aa347495a85d18d0d2f9e465fad8296c&pid=1-s2.0-S2772976124000205-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481220","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":"Male and female atria exhibit distinct acute electrophysiological responses to sex steroids","authors":"Simon P. Wells ,&nbsp;Christopher O'Shea ,&nbsp;Sarah Hayes ,&nbsp;Kate L. Weeks ,&nbsp;Paulus Kirchhof ,&nbsp;Lea M.D. Delbridge ,&nbsp;Davor Pavlovic ,&nbsp;James R. Bell","doi":"10.1016/j.jmccpl.2024.100079","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2024.100079","url":null,"abstract":"<div><p>The electrophysiological properties of the hearts of women and men are different. These differences are at least partly mediated by the actions of circulating estrogens and androgens on the cardiomyocytes. Experimentally, much of our understanding in this field is based on studies focusing on ventricular tissue, with considerably less known in the context of atrial electrophysiology. The aim of this investigation was to compare the electrophysiological properties of male and female atria and assess responses to acute sex steroid exposure. Age-matched adult male and female C57BL/6 mice were anesthetized (4 % isoflurane) and left atria isolated. Atria were loaded with Di-4-ANEPPS voltage sensitive dye and optical mapping performed to assess action potential duration (APD; at 10 %, 20 %, 30 %, 50 %, and 70 % repolarization) and conduction velocity in the presence of 1 nM and 100 nM 17β-estradiol or testosterone. Male and female left atria demonstrated similar baseline action potential duration and conduction velocity, with significantly greater APD₇₀ spatial heterogeneity evident in females. 17β-estradiol prolonged action potential duration in both sexes – an effect that was augmented in females. Atrial conduction was slowed in the presence of 100 nM 17β-estradiol in both males and females. Testosterone prolonged action potential duration in males only and did not modulate conduction velocity in either sex. This study provides novel insights into male and female atrial electrophysiology and its regulation by sex steroids. As systemic sex steroid levels change and intra-cardiac estrogen synthesis capacity increases with aging, these actions may have an increasingly important role in determining atrial arrhythmia vulnerability.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976124000199/pdfft?md5=7b1638d79694256323c8609806301439&pid=1-s2.0-S2772976124000199-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481262","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":"The cardiac blood transcriptome predicts de novo onset of atrial fibrillation in heart failure","authors":"Guillaume Lamirault ,&nbsp;Imen Fellah-Hebia ,&nbsp;Catherine Chevalier ,&nbsp;Isabelle Guisle ,&nbsp;Béatrice Guyomarc'h ,&nbsp;Aude Solnon ,&nbsp;Jean-Baptiste Gourraud ,&nbsp;Laurent Desprets ,&nbsp;Selim Abbey ,&nbsp;Christophe Leclercq ,&nbsp;Paul Bru ,&nbsp;Antoine Milhem ,&nbsp;Olivier Billon ,&nbsp;Frederic Anselme ,&nbsp;Arnaud Savouré ,&nbsp;Jean-Noël Trochu ,&nbsp;Rémi Houlgatte ,&nbsp;Gilles Lande ,&nbsp;Marja Steenman","doi":"10.1016/j.jmccpl.2024.100077","DOIUrl":"10.1016/j.jmccpl.2024.100077","url":null,"abstract":"<div><p>Heart failure (HF) increases the risk of developing atrial fibrillation (AF), leading to increased morbidity and mortality. Therefore, better prediction of this risk may improve treatment strategies. Although several predictors based on clinical data have been developed, the establishment of a transcriptome-based predictor of AF incidence in HF has proven to be more problematic. We hypothesized that the transcriptome profile of coronary sinus blood samples of HF patients is associated with AF incidence. We therefore enrolled 192 HF patients who were selected for biventricular cardioverter defibrillator implantation. Both coronary sinus and peripheral blood samples were obtained during the procedure. Patients were followed-up during two years and AF occurrence was based on interrogation of the defibrillator. A total of 96 patients stayed in sinus rhythm (SR) during follow-up, 13 patients developed AF within 1 year and 10 patients developed AF during the second year of follow up. Gene expression profiling of coronary sinus samples led to the identification of 321 AF predictor genes based on their differential expression between patients developing AF within 1 year of blood sampling and patients remaining in SR. The expression levels of these genes were combined to obtain a molecular atrial fibrillation prediction score for each patient which was significantly different between both patient groups (Mann-Whitney, <em>p</em> = 0.00018). We conclude that the cardiac blood transcriptome of HF patients should be further investigated as a potential AF risk prediction tool.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976124000175/pdfft?md5=b124ea86f7f6347dacfa628812a1629e&pid=1-s2.0-S2772976124000175-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141044623","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":"Dietary linoleic acid supplementation fails to rescue established cardiomyopathy in Barth syndrome","authors":"Siting Zhu ,&nbsp;Jing Pang ,&nbsp;Anh Nguyen ,&nbsp;Helen Huynh ,&nbsp;Sharon Lee ,&nbsp;Yusu Gu ,&nbsp;Frederic M. Vaz ,&nbsp;Xi Fang","doi":"10.1016/j.jmccpl.2024.100076","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2024.100076","url":null,"abstract":"<div><p>Barth syndrome (BTHS) is a mitochondrial lipid disorder caused by mutations in <em>TAFAZZIN</em> (<em>TAZ</em>), required for cardiolipin (CL) remodeling. Cardiomyopathy is a major clinical feature, with no curative therapy. Linoleic acid (LA) supplementation is proposed to ameliorate BTHS cardiomyopathy by enhancing linoleoyl group incorporation into CL. While the beneficial effect of dietary LA supplementation in delaying the development of BTHS cardiomyopathy has been recently tested, its potential to reverse established BTHS cardiomyopathy remains unclear. Our study revealed that LA supplementation cannot rescue established BTHS cardiomyopathy in mice, highlighting the importance of early initiation of LA supplementation for maximum benefits.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976124000163/pdfft?md5=3566cd05fb55958653c45205adb292c6&pid=1-s2.0-S2772976124000163-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140643864","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":"Monitoring mitochondrial calcium in cardiomyocytes during coverslip hypoxia using a fluorescent lifetime indicator","authors":"Yusuf Mastoor ,&nbsp;Mikako Harata ,&nbsp;Kavisha Silva ,&nbsp;Chengyu Liu ,&nbsp;Christian A. Combs ,&nbsp;Barbara Roman ,&nbsp;Elizabeth Murphy","doi":"10.1016/j.jmccpl.2024.100074","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2024.100074","url":null,"abstract":"<div><p>An increase in mitochondrial calcium via the mitochondrial calcium uniporter (MCU) has been implicated in initiating cell death in the heart during ischemia-reperfusion (I/R) injury. Measurement of calcium during I/R has been challenging due to the pH sensitivity of indicators coupled with the fall in pH during I/R. The development of a pH-insensitive indicator, mitochondrial localized Turquoise Calcium Fluorescence Lifetime Sensor (mito-TqFLITS), allows for quantifying mitochondrial calcium during I/R via fluorescent lifetime imaging. Mitochondrial calcium was monitored using mito-TqFLITS in neonatal mouse ventricular myocytes (NMVM) isolated from germline MCU-KO mice and MCU^fl/fl treated with CRE-recombinase to acutely knockout MCU. To simulate ischemia, a coverslip was placed on a monolayer of NMVMs to prevent access to oxygen and nutrients. Reperfusion was induced by removing the coverslip. Mitochondrial calcium increases threefold during coverslip hypoxia in MCU-WT. There is a significant increase in mitochondrial calcium during coverslip hypoxia in germline MCU-KO, but it is significantly lower than in MCU-WT. We also found that compared to WT, acute MCU-KO resulted in no difference in mitochondrial calcium during coverslip hypoxia and reoxygenation. To determine the role of mitochondrial calcium uptake via MCU in initiating cell death, we used propidium iodide to measure cell death. We found a significant increase in cell death in both the germline MCU-KO and acute MCU-KO, but this was similar to their respective WTs. These data demonstrate the utility of mito-TqFLITS to monitor mitochondrial calcium during simulated I/R and further show that germline loss of MCU attenuates the rise in mitochondrial calcium during ischemia but does not reduce cell death.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277297612400014X/pdfft?md5=dc4c42b415566e130d651438d6fd268c&pid=1-s2.0-S277297612400014X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140549542","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":"Roles of cMyBP-C phosphorylation on cardiac contractile dysfunction in db/db mice","authors":"Darshini A. Desai ,&nbsp;Akhil Baby ,&nbsp;Kalyani Ananthamohan ,&nbsp;Lisa C. Green ,&nbsp;Mohammed Arif ,&nbsp;Brittany C. Duncan ,&nbsp;Mohit Kumar ,&nbsp;Rohit R. Singh ,&nbsp;Sheryl E. Koch ,&nbsp;Sankar Natesan ,&nbsp;Jack Rubinstein ,&nbsp;Anil G. Jegga ,&nbsp;Sakthivel Sadayappan","doi":"10.1016/j.jmccpl.2024.100075","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2024.100075","url":null,"abstract":"<div><p>Type 2 diabetes mellitus (T2DM) is a metabolic disease and comorbidity associated with several conditions, including cardiac dysfunction leading to heart failure with preserved ejection fraction (HFpEF), in turn resulting in T2DM-induced cardiomyopathy (T2DM-CM). However, the molecular mechanisms underlying the development of T2DM-CM are poorly understood. It is hypothesized that molecular alterations in myopathic genes induced by diabetes promote the development of HFpEF, whereas cardiac myosin inhibitors can rescue the resultant T2DM-mediated cardiomyopathy. To test this hypothesis, a Leptin receptor-deficient <em>db/db</em> homozygous (Lepr <em>db/db</em>) mouse model was used to define the pathogenesis of T2DM-CM. Echocardiographic studies at 4 and 6 months revealed that Lepr db/db hearts started developing cardiac dysfunction by four months, and left ventricular hypertrophy with diastolic dysfunction was evident at 6 months. RNA-seq data analysis, followed by functional enrichment, revealed the differential regulation of genes related to cardiac dysfunction in Lepr <em>db/db</em> heart tissues. Strikingly, the level of cardiac myosin binding protein-C phosphorylation was significantly increased in Lepr <em>db/db</em> mouse hearts. Finally, using isolated skinned papillary muscles and freshly isolated cardiomyocytes, <em>CAMZYOS</em>® (mavacamten, MYK-461), a prescription heart medicine used for symptomatic obstructive hypertrophic cardiomyopathy treatment, was tested for its ability to rescue T2DM-CM. Compared with controls, MYK-461 significantly reduced force generation in papillary muscle fibers and cardiomyocyte contractility in the db/db group. This line of evidence shows that 1) T2DM-CM is associated with hyperphosphorylation of cardiac myosin binding protein-C and 2) MYK-461 significantly lessened disease progression <em>in vitro</em>, suggesting its promise as a treatment for HFpEF.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976124000151/pdfft?md5=02469e3592bb077b9cca064a6f7b5dab&pid=1-s2.0-S2772976124000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140540574","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":"Allele-specific dysregulation of lipid and energy metabolism in early-stage hypertrophic cardiomyopathy","authors":"Arpana Vaniya ,&nbsp;Anja Karlstaedt ,&nbsp;Damla Gulkok ,&nbsp;Tilo Thottakara ,&nbsp;Yamin Liu ,&nbsp;Sili Fan ,&nbsp;Hannah Eades ,&nbsp;Styliani Vakrou ,&nbsp;Ryuya Fukunaga ,&nbsp;Hilary J. Vernon ,&nbsp;Oliver Fiehn ,&nbsp;M. Roselle Abraham","doi":"10.1016/j.jmccpl.2024.100073","DOIUrl":"10.1016/j.jmccpl.2024.100073","url":null,"abstract":"<div><h3>Introduction</h3><p>Hypertrophic cardiomyopathy (HCM) results from pathogenic variants in sarcomeric protein genes that increase myocyte energy demand and lead to cardiac hypertrophy. However, it is unknown whether a common metabolic trait underlies cardiac phenotype at the early disease stage. To address this question and define cardiac biochemical pathology in early-stage HCM, we studied two HCM mouse models that express pathogenic variants in cardiac troponin T (<em>Tn</em><em>t2</em>) or myosin heavy chain (<em>M</em><em>yh6</em>) genes, and have marked differences in cardiac imaging phenotype, mitochondrial function at early disease stage.</p></div><div><h3>Methods</h3><p>We used a combination of echocardiography, transcriptomics, mass spectrometry-based untargeted metabolomics (GC-TOF, HILIC, CSH-QTOF), and computational modeling (CardioNet) to examine cardiac structural and metabolic remodeling at early disease stage (5 weeks of age) in R92W-TnT^+/− and R403Q-MyHC^+/− mutant mice. Data from mutants was compared with respective littermate controls (WT).</p></div><div><h3>Results</h3><p>Allele-specific differences in cardiac phenotype, gene expression and metabolites were observed at early disease stage. LV diastolic dysfunction was prominent in TnT mutants. Differentially-expressed genes in TnT mutant hearts were predominantly enriched in the Krebs cycle, respiratory electron transport, and branched-chain amino acid metabolism, whereas MyHC mutants were enriched in mitochondrial biogenesis, calcium homeostasis, and liver-X-receptor signaling. Both mutant hearts demonstrated significant alterations in levels of purine nucleosides, trisaccharides, dicarboxylic acids, acylcarnitines, phosphatidylethanolamines, phosphatidylinositols, ceramides and triglycerides; 40.4 % of lipids and 24.7 % of metabolites were significantly different in TnT mutants, whereas 10.4 % of lipids and 5.8 % of metabolites were significantly different in MyHC mutants. Both mutant hearts had a lower abundance of unsaturated long-chain acyl-carnitines (18:1, 18:2, 20:1), but only TnT mutants showed enrichment of FA18:0 in ceramide and cardiolipin species. CardioNet predicted impaired energy substrate metabolism and greater phospholipid remodeling in TnT mutants than in MyHC mutants.</p></div><div><h3>Conclusions</h3><p>Our systems biology approach revealed marked differences in metabolic remodeling in R92W-TnT and R403Q-MyHC mutant hearts, with TnT mutants showing greater derangements than MyHC mutants, at early disease stage. Changes in cardiolipin composition in TnT mutants could contribute to impairment of energy metabolism and diastolic dysfunction observed in this study, and predispose to energetic stress, ventricular arrhythmias under high workloads such as exercise.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976124000138/pdfft?md5=f1f0a6ddc74aacec9f7b7ead394d95f3&pid=1-s2.0-S2772976124000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140398579","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":"The selective serotonin reuptake inhibitor paroxetine improves right ventricular systolic function in experimental pulmonary hypertension","authors":"Mark T. Waddingham ,&nbsp;Hirotsugu Tsuchimochi ,&nbsp;Takashi Sonobe ,&nbsp;Vasco Sequeira ,&nbsp;Md Junayed Nayeem ,&nbsp;Mikiyasu Shirai ,&nbsp;James T. Pearson ,&nbsp;Takeshi Ogo","doi":"10.1016/j.jmccpl.2024.100072","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2024.100072","url":null,"abstract":"<div><h3>Background</h3><p>Pulmonary hypertension (PH) often leads to right ventricle (RV) failure, a significant cause of morbidity and mortality. Despite advancements in PH management, progression to RV maladaptation and subsequent failure remain a clinical challenge. This study explored the effect of paroxetine, a selective serotonin reuptake inhibitor (SSRI), on RV function in a rat model of PH, hypothesizing that it improves RV function by inhibiting G protein-coupled receptor kinase 2 (GRK2) and altering myofilament protein phosphorylation.</p></div><div><h3>Methods</h3><p>The Su5416/hypoxia (SuHx) rat model was used to induce PH. Rats were treated with paroxetine and compared to vehicle-treated and control groups. Parameters measured included RV morphology, systolic and diastolic function, myofilament protein phosphorylation, GRK2 activity, and sympathetic nervous system (SNS) markers.</p></div><div><h3>Results</h3><p>Paroxetine treatment significantly improved RV systolic function, evidenced by increased stroke volume, cardiac output, and ejection fraction, without significantly affecting RV hypertrophy, myosin heavy chain/titin isoform switching, or fibrosis. Enhanced phosphorylation of titin and myosin light chain-2 was observed, correlating positively with improved systolic function. Contrary to the hypothesis, improvements occurred independently of GRK2 inhibition or SNS modulation, suggesting an alternate mechanism, potentially involving antioxidant properties of paroxetine.</p></div><div><h3>Conclusion</h3><p>Paroxetine improves RV systolic function in PH rats, likely through mechanisms beyond GRK2 inhibition, possibly related to its antioxidant effects. This highlights the potential of paroxetine in managing RV dysfunction in PH, warranting further investigation into its detailed mechanisms of action and clinical applicability.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976124000126/pdfft?md5=69eb8d8b649d066927e31fc6a2eb106c&pid=1-s2.0-S2772976124000126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295916","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":"Endothelial identity not found – Beyond passage 38, commercial cardiac microvascular endothelial cells do not express CD31 and VE-cadherin","authors":"Sarah Hilderink,&nbsp;Jolanda van der Velden,&nbsp;Diederik W.D. Kuster","doi":"10.1016/j.jmccpl.2024.100071","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2024.100071","url":null,"abstract":"<div><p>Few immortalized cardiac microvascular endothelial cell (CMEC) lines are available, particularly mouse lines. We purchased the CLU510 mCMEC line (Cedarlane), isolated by fluorescence-activated cell sorting for CD31 and VE-cadherin. The cell line has been used in previous studies, although none report CD31 or VE-cadherin expression. We analyzed endothelial profile of two vials of passage 38 cells. CD31 and VE-cadherin mRNA were hardly expressed in mCMECs compared to primary mouse lung ECs. CD31 and VE-cadherin protein levels were also negligible compared to multiple EC lines. Thus, CLU510 mCMECs beyond P38 do not harbor an endothelial phenotype. Caution should be warranted when using commercial cells and journals should carefully consider the validity of results when essential characterization of cell lines is omitted.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976124000114/pdfft?md5=8aadad523d6cea7d8433fe2ecea150e7&pid=1-s2.0-S2772976124000114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140180356","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":"Treatment with αvβ3-integrin-specific 29P attenuates pressure-overload induced cardiac remodelling after transverse aortic constriction in mice","authors":"Alexandra Njegić ,&nbsp;Lina Laid ,&nbsp;Min Zi ,&nbsp;Eleni Maniati ,&nbsp;Jun Wang ,&nbsp;Alexandru Chelu ,&nbsp;Laura Wisniewski ,&nbsp;Jenna Hunter ,&nbsp;Sukhpal Prehar ,&nbsp;Nicholas Stafford ,&nbsp;Chaim Gilon ,&nbsp;Amnon Hoffman ,&nbsp;Michael Weinmüller ,&nbsp;Horst Kessler ,&nbsp;Elizabeth J. Cartwright ,&nbsp;Kairbaan Hodivala-Dilke","doi":"10.1016/j.jmccpl.2024.100069","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2024.100069","url":null,"abstract":"<div><p>Heart failure remains one of the largest clinical burdens globally, with little to no improvement in the development of disease-eradicating therapeutics. Integrin targeting has been used in the treatment of ocular disease and cancer, but little is known about its utility in the treatment of heart failure. Here we sought to determine whether the second generation orally available, αvβ3-specific RGD-mimetic, <strong><em>29P</em></strong>, was cardioprotective. Male mice were subjected to transverse aortic constriction (TAC) and treated with 50 μg/kg <strong><em>29P</em></strong> or volume-matched saline as Vehicle control. At 3 weeks post-TAC, echocardiography showed that <strong><em>29P</em></strong> treatment significantly restored cardiac function and structure indicating the protective effect of <strong><em>29P</em></strong> treatment in this model of heart failure. Importantly, <strong><em>29P</em></strong> treatment improved cardiac function giving improved fractional shortening, ejection fraction, heart weight and lung weight to tibia length fractions, together with partial restoration of Ace and Mme levels, as markers of the TAC insult. At a tissue level, <strong><em>29P</em></strong> reduced cardiomyocyte hypertrophy and interstitial fibrosis, both of which are major clinical features of heart failure. RNA sequencing identified that, mechanistically, this occurred with concomitant alterations to genes involved molecular pathways associated with these processes such as metabolism, hypertrophy and basement membrane formation. Overall, targeting αvβ3 with <strong><em>29P</em></strong> provides a novel strategy to attenuate pressure-overload induced cardiac hypertrophy and fibrosis, providing a possible new approach to heart failure treatment.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772976124000096/pdfft?md5=7c76dfb468157ae5244d4c1a01611ff7&pid=1-s2.0-S2772976124000096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140145162","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}