MicroRNA-221/222 Family Counteracts Myocardial Fibrosis in Pressure Overload-Induced Heart FailureNovelty and Significance [Heart]
Pressure overload causes cardiac fibroblast activation and transdifferentiation, leading to increased interstitial fibrosis formation and subsequently myocardial stiffness, diastolic and systolic dysfunction, and eventually heart failure. A better understanding of the molecular mechanisms underlying pressure overload–induced cardiac remodeling and fibrosis will have implications for heart failure treatment strategies. The microRNA (miRNA)-221/222 family, consisting of miR-221-3p and miR-222-3p, is differentially regulated in mouse and human cardiac pathology and inversely associated with kidney and liver fibrosis. We investigated the role of this miRNA family during pressure overload–induced cardiac remodeling. In myocardial biopsies of patients with severe fibrosis and dilated cardiomyopathy or aortic stenosis, we found significantly lower miRNA-221/222 levels as compared to matched patients with nonsevere fibrosis. In addition, miRNA-221/222 levels in aortic stenosis patients correlated negatively with the extent of myocardial fibrosis and with left ventricular stiffness. Inhibition of both miRNAs during AngII (angiotensin II)–mediated pressure overload in mice led to increased fibrosis and aggravated left ventricular dilation and dysfunction. In rat cardiac fibroblasts, inhibition of miRNA-221/222 derepressed TGF-β (transforming growth factor-β)–mediated profibrotic SMAD2 (mothers against decapentaplegic homolog 2) signaling and downstream gene expression, wherea...
Source: Hypertension - Category: Cardiology Authors: Robin Verȷans, Tim Peters, Francisco Javier Beaumont, Rick van Leeuwen, Tessa van Herwaarden, Wouter Verhesen, Chantal Munts, Mitchell Biȷnen, Michiel Henkens, Javier Diez, Leon J. de Windt, Frans A. van Nieuwenhoven, Marc van Bilsen, Marie Tags: Basic Science Research, Cell Signaling/Signal Transduction, Fibrosis, Heart Failure, Remodeling Original Articles Source Type: research
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