Fibroblast Activation Protein Compared with Other Markers of Activated Smooth Muscle Cells, Extracellular Matrix Turnover and Inflammation in a Mouse Model of Atherosclerosis

<b>Background:</b> Fibroblast activation protein (FAP) is a cell surface glycoprotein expressed by myofibroblastic cells in areas of active tissue remodeling, such as wound healing, fibrosis, and certain chronic inflammatory lesions. As FAP is uniquely present in chronic inflammatory lesions and has an important role in extracellular matrix (ECM) turnover, it appears to have all the characteristics necessary for involvement in atherosclerosis and atherosclerotic plaque rupture and has become a potential target in the treatment of myocardial infarction. <b>Methods:</b> To further understand the role of FAP, its expression in atherosclerotic plaques was examined in a genetically modified mouse model of accelerated atherosclerosis (<i>Apobec1</i> −/− <i>Ldlr</i> −/− double-knockout mice). The immunohistochemical Fap staining of atherosclerotic plaques in a mouse model of atherosclerosis was correlated with quantification of <i>Fap</i> mRNA obtained from the atherosclerotic plaques of the aortic arch. Fap distribution was characterized in mouse atherosclerotic plaques relative to other markers of activated smooth muscle cells, such as alpha smooth muscle actin and myosin heavy chain (Acta2 and Myh2), ECM turnover (Ki-67, procollagen III and Mmp-9), and inflammation in atherosclerosis (Cd-44, Il-12 and Tgf beta) using immunohistochemistry (IH) and RT-PCR analysis. <b>Results:</b> The mouse model of accelerated atherosclerosis showed an increasing presence of Fap with the progression of atherosclerosis and a high expression level in advanced atherosclerotic lesions compared with other markers of ECM turnover and inflammation in atherosclerosis. <b>Conclusions:</b> FAP exhibits a distinct pattern of expression in a mouse model of atherosclerosis as compared to other markers of activated vascular smooth muscle cells, ECM degeneration, and inflammatory cytokines.