Study of secretomes from atheroma plaques: comparative proteomic analysis of atheroma plaque-derived exosomes with either induced or inhibited neovascularization

Abstract

Atherosclerosis is a pathologic event that involves a degenerative progression of the endothelium where chronic inflammatory response, fibroproliferation and angiogenesis are observed. Angiogenesis role in the plaque formation process is due an unbalance of pro- and anti-angiogenic factors, resulting in neovascularization during atheroma formation. This neovascularization stimulus promotes sprouting of immature, fragile blood vessels though. Inflammatory and angiogenesis processes are strongly correlated to macrophage infiltration and plaque rupture. Inflammatory response and high microvessel density seem to be more crucial than plaque size when it comes to plaque instability. Both microvasculature formation and inflammatory progression are mediated by soluble factors and exosomes, which together modulate the atheroma plaque microenvironment. Proteomic analysis has the advantage of being a methodology able to screen, identify and provide information on the regulation of several proteins at the same time in a given system. The present study aims the proteomic analysis of atheroma plaque-derived exosomes linked to angiogenesis and atherogenesis, the identification of potential biomarkers of atherosclerotic lesions and use of exosomes in therapeutics. Atherosclerosis and angiogenesis related-exosomes identification by proteomics study will be carried out using "in vitro" models and validated through serum samples analysis from high risk cardiovascular disease (CVD) subjects. (AU)