Opposing Actions of Fibroblast and Cardiomyocyte Smad3 Signaling in the Infarcted Myocardium

• DOI: 10.1161/circulationaha.117.029622
• Publication Date: 2017-12-11T10:30:11Z
• Authors: Ping Kong; Arti V. Shinde; Ya Su; Ilaria Russo; Bijun Chen; Amit Saxena; Simon J. Conway; Jonathan M. Graff; Nikolaos G. Frang...
• Keywords: Myofibroblast; Sirius Red

Transforming growth factor-βs regulate a wide range of cellular responses by activating Smad-dependent and Smad-independent cascades. In the infarcted heart, Smad3 signaling is activated in both cardiomyocytes interstitial cells. We hypothesized that cell-specific actions repair remodeling myocardium.To dissect myocardial infarction, we generated mice with loss fibroblasts or cardiomyocytes. Cardiac function was assessed after reperfused nonreperfused infarction using echocardiography. The effects on heart were studied histological studies, assessment protein, gene expression levels. vitro, isolated cardiac fibroblasts.Mice fibroblast-specific had accentuated adverse exhibited an increased incidence late rupture infarction. consequences not result acute infarct size but associated unrestrained fibroblast proliferation, impaired scar remodeling, reduced fibroblast-derived collagen synthesis, perturbed alignment myofibroblast arrays infarct. Polarized light microscopy Sirius red-stained sections demonstrated changes morphology organization collagenous matrix area. contrast, α-smooth muscle actin myofibroblasts affected loss. critically regulated function, integrin-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX-2) expression. attenuated dysfunction Cardiomyocyte-specific did affect cardiomyocyte apoptosis myocardium, accompanied decreased NOX-2 levels, nitrosative stress, lower metalloproteinase-2 expression.In healing myofibroblast- cardiomyocyte-specific activation has contrasting functional outcomes may involve integrin/reactive oxygen axis.