Analysis of Protein Expression Differences in Cardiac Fibroblasts Isolated from 7-day Sham-operated and Infarcted Murine Hearts

Myocardial infarction (MI) induces cardiac remodeling, activation of cardiac fibroblasts (CFs), reduced tissue compliance, and heart failure progression. To identify novel mediators of cardiac fibrosis, we conducted mass spectrometry on CFs isolated by pre-plating or fluorescence activated cell sorting (FACs) from 7-day sham and infarcted mouse hearts. Pre-plated CFs from infarcted and remote regions showed that CFs were enriched similarly in proteins associated with myofibroblast activation and profibrotic signaling, including cell-cell/matrix adhesion, protein folding, and collagen organization. Thus, MI causes more global effects on CF activation than were previously understood. Using a fibroblast reporter mouse (Col1α1-GFP/αSMA-dsRED), αSMA- and αSMA+ CFs were isolated by FACs from 7-day sham and infarcted hearts to examine potential differences in the response of these two CF populations to ischemic injury. Surprisingly, greater differences were observed in sham compared to infarcted hearts, suggesting that cardiac injury induced convergence of all CFs towards a more profibrotic phenotype.M.Sc