Journal of molecular and cellular cardiology plus最新文献

{"title":"Myocardial overexpression of protein phosphatase 2A-B56α improves resistance against ischemia-reperfusion injury","authors":"Julius R. Herting ,&nbsp;Anna M. Berg ,&nbsp;Katarina Hadova ,&nbsp;Alexander Heinick ,&nbsp;Simone König ,&nbsp;Michael Kuhlmann ,&nbsp;Frank U. Müller ,&nbsp;Uwe Kirchhefer","doi":"10.1016/j.jmccpl.2022.100030","DOIUrl":"10.1016/j.jmccpl.2022.100030","url":null,"abstract":"<div><p>Protein phosphatase 2A (PP2A) plays a central role in myocardial ischemia-reperfusion (I/R) injury. Several studies showed a detrimental function of PP2A by using either overexpression models of the catalytic subunit (PP2Ac) or exogenous inhibitors of PP2Ac. However, all of these approaches underestimate the contribution of regulatory B subunits in modulating the PP2A holoenzyme. To better understand the influence of B subunits on a “controlled” regulation of PP2A, we tested a mouse model overexpressing PP2A-B56α (TG) in the heart under the conditions of I/R in comparison to wild-type littermates (WT). Contractility was increased after reperfusion in isolated TG hearts that were initially subjected to a 20-min no-flow ischemia. This was associated with lower phosphorylation levels of myosin-binding protein C and the ryanodine receptor 2 in TG compared to WT. The application of okadaic acid abolished the contractile and biochemical effects in TG hearts. Moreover, reperfusion resulted in the detection of higher PP2A-B56α levels in mitochondrial preparations of TG hearts. The phosphorylation of ERK1 was increased in the early reperfusion phase in TG compared to WT hearts corresponding to a transient attenuation of PP2A activity. Ischemia led to a prolonged contracture time in TG hearts and a lower acidification in isolated TG cardiomyocytes. The formation of interstitial fibrosis by transient ligation of the left anterior descending (LAD) artery was reduced in TG compared to WT hearts. Taken together, these findings indicate that overexpression of PP2A-B56α is protective against I/R injury and that B56α merits further investigation as a potential therapeutic target.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41675230","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}

{"title":"MicroRNA miR-378-3p is a novel regulator of endothelial autophagy and function","authors":"Shuhan Bu ,&nbsp;Jameela J. Joseph ,&nbsp;Hien C. Nguyen ,&nbsp;Mehroz Ehsan ,&nbsp;Berk Rasheed ,&nbsp;Aman Singh ,&nbsp;Mohammad Qadura ,&nbsp;Jefferson C. Frisbee ,&nbsp;Krishna K. Singh","doi":"10.1016/j.jmccpl.2022.100027","DOIUrl":"10.1016/j.jmccpl.2022.100027","url":null,"abstract":"<div><p>Autophagy is a highly conserved cellular process in which cytoplasmic materials are internalized into an autophagosome that later fuses with a lysosome for their degradation and recycling. MicroRNAs (miRNAs) are integral regulators in various cellular processes including autophagy and endothelial function. Accordingly, we hypothesize that miRNA, miR-378-3p, is an essential regulator of endothelial autophagy and endothelial function. MiR-378-3p expression was measured following inhibition and activation of autophagy in endothelial cells. A gain- or loss-of function approach was employed to either overexpress or inhibit the expression of miR-378-3p, respectively, in cultured endothelial cells, and markers of autophagy and indices of endothelial function, such as proliferation, migration and tube forming potential were measured. Inhibition and activation of autophagy up- and down-regulated the expression of miR-378-3p, respectively. Furthermore, miR-378a-3p overexpression was associated with impaired autophagy indicated by a reduced LC3-II/LC3-I ratio, and endothelial function indicated by increased proliferation associated with reduced p21 expression, reduced angiogenic potential and increased migration, which were associated with reduced expression of endothelial nitric oxide synthase (eNOS), an essential regulator of endothelial function. Accordingly, miR-378a-3p inhibition was associated with reduced cell proliferation, migration and increased eNOS in endothelial cells. Apoptosis was not affected in cells transfected with antagomir. Using <em>in silico</em> approach, <em>Protein Disulfide Isomerase Family A Member 4</em> (PDIA-4) was identified and confirmed as a target of miR-378-3p. PDIA-4 expression was significantly reduced or enhanced in miR-378-3p-overexpressing or -silenced endothelial cells, respectively. Our findings show an inverse relationship between miR-378-3p and endothelial autophagy and function, providing a novel insight about the epigenetic regulation of these processes.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46069951","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}

{"title":"Knockout of ACE-N facilitates improved cardiac function after myocardial infarction","authors":"Hamid Suhail ,&nbsp;Hongmei Peng ,&nbsp;Jiang Xu ,&nbsp;Hani N. Sabbah ,&nbsp;Khalid Matrougui ,&nbsp;Tang-Dong Liao ,&nbsp;Pablo A. Ortiz ,&nbsp;Kenneth E. Bernstein ,&nbsp;Nour-Eddine Rhaleb","doi":"10.1016/j.jmccpl.2022.100024","DOIUrl":"10.1016/j.jmccpl.2022.100024","url":null,"abstract":"<div><p>Angiotensin-converting enzyme (ACE) hydrolyzes <em>N</em>-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) into inactive fragments through its N-terminal site (ACE<img>N). We previously showed that Ac-SDKP mediates ACE inhibitors' cardiac effects. Whether increased bioavailability of endogenous Ac-SDKP caused by knocking out ACE-N also improves cardiac function in myocardial infarction (MI)-induced heart failure (HF) is unknown. Wild-type (WT) and ACE-N knockout (ACE-NKO) mice were subjected to MI by ligating the left anterior descending artery and treated with vehicle or Ac-SDKP (1.6 mg/kg/day, s.c.) for 5 weeks, after which echocardiography was performed and left ventricles (LV) were harvested for histology and molecular biology studies. ACE-NKO mice showed increased plasma Ac-SDKP concentrations in both sham and MI group compared to WT. Exogenous Ac-SDKP further increased its circulating concentrations in WT and ACE-NKO. Shortening (SF) and ejection (EF) fractions were significantly decreased in both WT and ACE-NKO mice post-MI, but ACE-NKO mice exhibited significantly lesser decrease. Exogenous Ac-SDKP ameliorated cardiac function post-MI only in WT but failed to show any additive improvement in ACE-NKO mice. Sarcoendoplasmic reticulum calcium transport ATPase (SERCA2), a marker of cardiac function and calcium homeostasis, was significantly decreased in WT post-MI but rescued with Ac-SDKP, whereas ACE-NKO mice displayed less loss of SERCA2 expression. Our study demonstrates that gene deletion of ACE-N resulted in improved LV cardiac function in mice post-MI, which is likely mediated by increased circulating Ac-SDKP and minimally reduced expression of SERCA2. Thus, future development of specific and selective inhibitors for ACE-N could represent a novel approach to increase endogenous Ac-SDKP toward protecting the heart from post-MI remodeling.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/11/nihms-1863007.PMC9910327.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10871677","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":"ITCH puts the brakes on septic cardiomyopathy","authors":"Dominic P. Del Re ,&nbsp;Qinghang Liu","doi":"10.1016/j.jmccpl.2022.100019","DOIUrl":"10.1016/j.jmccpl.2022.100019","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/S2772976122000137/pdfft?md5=28431ff2c0547acb192ee3e0193652dd&pid=1-s2.0-S2772976122000137-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49148705","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":"Positive aspects of negative data","authors":"David Eisner","doi":"10.1016/j.jmccpl.2022.100016","DOIUrl":"10.1016/j.jmccpl.2022.100016","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/S2772976122000101/pdfft?md5=5d43b7ab8f857fb1a14124a656aafdda&pid=1-s2.0-S2772976122000101-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41399702","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":"Cardiac-specific ITCH overexpression ameliorates septic cardiomyopathy via inhibition of the NF-κB signaling pathway","authors":"Yuji Saito,&nbsp;Yoichiro Otaki,&nbsp;Tetsu Watanabe,&nbsp;Shingo Tachibana,&nbsp;Junya Sato,&nbsp;Yuta Kobayashi,&nbsp;Tomonori Aono,&nbsp;Jun Goto,&nbsp;Masahiro Wanezaki,&nbsp;Daisuke Kutsuzawa,&nbsp;Shigehiko Kato,&nbsp;Harutoshi Tamura,&nbsp;Satoshi Nishiyama,&nbsp;Takanori Arimoto,&nbsp;Hiroki Takahashi,&nbsp;Masafumi Watanabe","doi":"10.1016/j.jmccpl.2022.100018","DOIUrl":"10.1016/j.jmccpl.2022.100018","url":null,"abstract":"<div><h3>Background</h3><p>Septic cardiomyopathy is a common complication of septic shock and organ dysfunction. ITCH is a HECT (homologous to the E6-AP carboxyl-terminus)-type ubiquitin E3 ligase that plays a critical role in inflammatory suppression. Herein, we focused on the interaction between ITCH and key regulators of nuclear factor-κB (NF-κB), such as tumor necrosis factor receptor-associated factor 6 (TRAF6) and transforming growth factor-β activated kinase 1 (TAK1), and examined the impact of ITCH on the development of septic cardiomyopathy.</p></div><div><h3>Methods and results</h3><p>In H9C2 cardiomyocytes, ITCH protein expression decreased in response to lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα). The protein interactions of ITCH with TRAF6 and TAK1 were confirmed by immunoprecipitation <em>in vitro</em> and <em>in vivo</em>. Based on overexpression and knockdown studies of ITCH in H9C2 cardiomyocytes, ITCH regulates the phosphorylation of NF-κB and subsequent interleukin 6 (<em>IL-6</em>) expression in response to LPS and TNFα stimulation. LPS was intraperitoneally injected into transgenic mice with cardiac-specific overexpression of ITCH (ITCH-Tg) and wild-type (WT) mice. Compared with WT mice, phosphorylation of NF-κB and subsequent <em>IL-6</em> expression were inhibited in ITCH-Tg mice. Cardiac systolic dysfunction after LPS administration was ameliorated in ITCH-Tg mice, and the survival rate was higher in ITCH-Tg mice than in WT mice.</p></div><div><h3>Conclusion</h3><p>ITCH interacts with TRAF6 and TAK1 in cardiomyocytes and improves cardiac function and survival rates in septic cardiomyopathy by suppressing the NF-κB pathway.</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/S2772976122000125/pdfft?md5=39a90ca15ede55556beb77790ae75b65&pid=1-s2.0-S2772976122000125-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48792544","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":"“Reproducibility and reporting of negative results in cardiovascular research” from the perspective of mid-career investigator","authors":"Ippei Shimizu","doi":"10.1016/j.jmccpl.2022.100017","DOIUrl":"10.1016/j.jmccpl.2022.100017","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/S2772976122000113/pdfft?md5=dfa633d305171b737f383b1dbe7bb7bf&pid=1-s2.0-S2772976122000113-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42249838","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 effect of moderate intensity aerobic exercise on cardiovascular function, cardiorespiratory fitness and estrogen receptor alpha gene in overweight/obese postmenopausal women: A randomized controlled trial","authors":"Abbas Malandish ,&nbsp;Mohammad Rahmati-Yamchi","doi":"10.1016/j.jmccpl.2022.100026","DOIUrl":"10.1016/j.jmccpl.2022.100026","url":null,"abstract":"<div><h3>Objective</h3><p>The purpose of this study was to examine the effect of 12 weeks of moderate intensity aerobic exercise on echocardiographic and cardiorespiratory fitness (CRF) parameters, lymphocyte estrogen receptor alpha (ERα) gene expression and sex hormones (17β-estradiol and progesterone) in overweight/obese postmenopausal women (OPMW).</p></div><div><h3>Methods</h3><p>Twenty-seven sedentary OPMW aged 45 to 65 years old were randomly assigned to exercise (EX, n = 14) and control (C, n = 13) groups. The EX group performed warm up-walking/jogging moderate intensity aerobic exercise program- recovery (60 min/day, 3 days/week at 70 % of maximal heart rate reserve for 12 weeks) while the C group participated in no intervention and maintained their daily physical activity level, sedentary normal lifestyle and dietary habits during 12-week. The lymphocyte ERα gene expression, serum levels of 17β-estradiol and progesterone, and CRF &amp; echocardiographic parameters were measured at baseline and week-12.</p></div><div><h3>Results</h3><p>After 12-week, the increase in ERα gene expression (p = 0.009, estimate of effect size/Eta = 28.2 %), VO_2max (p = 0.001, Eta = 53.4 %), walking-jogging time to exhaustion (WJTE) (p = 0.001, Eta = 55.1 %), metabolic equivalent of task (METs) (p = 0.001, Eta = 97.9 %), left ventricular ejection fraction (LVEF) (p = 0.001, Eta = 53.6 %), cardiac output (Q) (p = 0.036, Eta = 22.3 %), and cardiac index (p = 0.030, Eta = 22.5 %) were significantly higher in the EX group compared to the C group, whereas body fat (p = 0.023, Eta = 25.7 %), left ventricular end-systolic diameter (LVESD) (p = 0.013, Eta = 28.3 %), and mitral E-wave deceleration time (E-wave D time) (p = 0.007, Eta = 32.1 %) were significantly decreased.</p></div><div><h3>Conclusions</h3><p>The results suggested that moderate intensity aerobic exercise can be improved cardiac function such as LVEF, Q, cardiac index, LVESD, and E-wave D time, CRF, ERα-mRNA gene expression as well as maintained sex hormones among sedentary OPMW during menopause, as these positive cellular and molecular or physiological adaptations may be signs of cardioprotective effects by aerobic exercise.</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/S2772976122000204/pdfft?md5=55f7aa4a3d703528361a45a03f9b6741&pid=1-s2.0-S2772976122000204-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54552816","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":"Reproducibility and reporting negative data","authors":"Jolanda van der Velden","doi":"10.1016/j.jmccpl.2022.100021","DOIUrl":"10.1016/j.jmccpl.2022.100021","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/S2772976122000150/pdfft?md5=c263e8ad2dfa7f576691fd79af7e43b4&pid=1-s2.0-S2772976122000150-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42229291","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":"Transcriptomics reveal stretched human pluripotent stem cell-derived cardiomyocytes as an advantageous hypertrophy model","authors":"Lotta Pohjolainen,&nbsp;Heikki Ruskoaho,&nbsp;Virpi Talman","doi":"10.1016/j.jmccpl.2022.100020","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2022.100020","url":null,"abstract":"<div><p>Left ventricular hypertrophy, characterized by hypertrophy of individual cardiomyocytes, is an adaptive response to an increased cardiac workload that eventually leads to heart failure. Previous studies using neonatal rat ventricular myocytes (NRVMs) and animal models have revealed several genes and signaling pathways associated with hypertrophy and mechanical load. However, these models are not directly applicable to humans. Here, we studied the effect of cyclic mechanical stretch on gene expression of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using RNA sequencing. hiPSC-CMs showed distinct hypertrophic changes in gene expression at the level of individual genes and in biological processes. We also identified several differentially expressed genes that have not been previously associated with cardiomyocyte hypertrophy and thus serve as attractive targets for future studies. When compared to previously published data attained from stretched NRVMs and human embryonic stem cell-derived cardiomyocytes, hiPSC-CMs displayed a smaller number of changes in gene expression, but the differentially expressed genes revealed more pronounced enrichment of hypertrophy-related biological processes and pathways. Overall, these results establish hiPSC-CMs as a valuable <em>in vitro</em> model for studying human cardiomyocyte hypertrophy.</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/S2772976122000149/pdfft?md5=f0b59c3f50b0a71a7732d13d1addd192&pid=1-s2.0-S2772976122000149-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137342231","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}