Abstract MP259: The Role Of Sertad4 In Pathological Cardiac Remodeling
| العنوان: | Abstract MP259: The Role Of Sertad4 In Pathological Cardiac Remodeling |
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| المؤلفون: | Federica Accornero, Alessandro Canella, Erin McGrail, Lynn Marcho, Bryan A. Whitson, Richard J. Gumina, Shamama Nishat, Matthew S. Stratton, Ashley Francois, Oscar Bermeo-Blanco, Paul M.L. Janssen |
| المصدر: | Circulation Research. 129 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Pathology, medicine.medical_specialty, Physiology, business.industry, medicine, Cardiology and Cardiovascular Medicine, business, Pathological |
| الوصف: | Over 6 million Americans suffer from heart failure (HF) while the 5-year mortality rate following first admission for HF is over 40%. Cardiac fibrosis is a clinical hallmark of HF, regardless of the initiating pathology and is thought to contribute to disease progression. Using an epigenomics discovery approach, we uncovered a nuclear protein, Sertad4, as a potential anti-fibrotic target. Our data indicate that Sertad4 is a positive regulator of fibroblast activation. Specifically, cultured cardiac fibroblast experiments demonstrate that Sertad4 targeting with shRNAs blocks fibroblast proliferation and causes cells to arrest in the G2/M phase of the cell cycle. Also, shRNA targeting of Sertad4 dramatically blocked activation of myofibroblast differentiation genes (αSMA/POSTN/COL1A1). Mechanistically, these effects appear to be mediated by Sertad4 regulation of SMAD2 protein stability in the presence of TGF-β1 stimulation as demonstrated by proteasome inhibition experiments. RNA-seq analysis indicate that Sertad4 also regulates the expression of genes involved in ubiquitination and proteasome degradation. Next, we sought to determine the effect of global Sertad4 knockout on post-myocardial infarct (MI) remodeling and cardiac function in mice. After 4 weeks of permanent LAD ligation, echocardiography was performed to measure systolic function. Relative to wild-type (WT) controls, the Sertad4 KO mice showed preserved systolic function as evident by improved ejection fraction (WT 14.4 +/- 3.6 vs. KO 33.9+/-5.9, p=0.035) and fractional shortening (WT 6.5 +/- 1.7 vs. KO 16.4 +/- 3.4, p=0.046). β-gal staining in the Sertad4/LacZ reporter mouse subjected to MI showed robust Sertad4/LacZ expression in the ischemic scar and boarder-zone with almost no expression in control hearts. This data supports the notion that Sertad4 has a key role in cardiac remodeling in response to ischemic injury. |
| تدمد: | 1524-4571 0009-7330 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::28d448873b7ab67c21bb0c3e5acc0c2e https://doi.org/10.1161/res.129.suppl_1.mp259 |
| رقم الأكسشن: | edsair.doi...........28d448873b7ab67c21bb0c3e5acc0c2e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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