Overview of Current Proteomic Approaches for Discovery of Vascular Biomarkers of Atherosclerosis

Abstract

Cardiovascular diseases are the leading cause of mortality and morbidity in developed countries being atherosclerosis the major contributor. Atherosclerosis is a form of chronic inflammation characterized by the accumulation of lipids and fibrous elements in medium and large arteries (Libby, 2002). The retention of apoB-100 containing lipoproteins (mainly LDL and Lp(a)) in the subendothelial space and their subsequent oxidation is thought to be the leading event in the development of atherosclerotic lesions (Williams & Tabas, 1995). The degree of inflammation, proteolysis, calcification and neovascularization affects the stability of advanced lesions. Plaque rupture and thrombosis are the most important clinical complications in the pathogenesis of stroke, coronary arteries and peripheral vascular diseases (Lutgens et al., 2003). So, the identification of early biomarkers of plaque presence and susceptibility to ulceration could be of primary importance in preventing such a lifethreatening event. Disease aetiology is very complex and includes several important environmental and genetic risk factors such as hyperlipidemia, diabetes, and hypertension. In this regard elevated plasma levels of LDL cholesterol and low levels of HDL cholesterol have been long associated with the onset and development of atherosclerotic lesions. Although enormous efforts have been done to elucidate the molecular mechanisms underlying plaque formation and progression, they are not yet completely understood. In the last years, proteomic studies have been undertaken to both elucidate pathways of atherosclerotic degeneration and individuate new circulating markers to be utilized either as early diagnostic traits or as targets for new drug therapies. This chapter will provide an overview of latest advances in proteomic studies on atherosclerosis and some related diseases, with particular emphasis on vascular tissue proteomics and lipoproteomics.