Identification And Putative Function Of Fibroblast Activation Protein And Relevance To Post-Myocardial Infarction Remodeling

Background: While changes in extracellular matrix (ECM) structure and function contribute to adverse ventricular (LV) remodeling with myocardial infarction (MI), the integration of cellular (fibroblast; FIBRO) and proteolytic (matrix metalloproteinases, MMPs) with respect to localized activation pathways remains poorly understood. Transformed FIBROs, such as cancer associated FIBROs, have been shown to express a transmembrane serine protease, fibroblast activation protein (FAP). However, whether and to what degree FAP is expressed within the MI, is associated with FIBROs, and functionality in the context of MMP activation remained unclear. Methods and Results: MI was induced in adult pigs (14 days, coronary ligation, n=5), whereby LV end-diastolic volume increased from baseline (40±1 vs 68±2 mL, pu003c0.05), consistent with adverse LV remodeling. FAP expression (rtPCR) within the MI increased by 7-fold compared to the identical LV region from referent control pigs (n=4). FIBROs isolated from the MI/control re...