Quest for Novel Cardiovascular Biomarkers by Proteomic Analysis

Abstract

Atherosclerosis, and the resulting coronary heart disease and stroke, is the most common cause of death in developed countries. Atherosclerosis is an inflammatory process that results in the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction (MI) and stroke. Although certain risk factors (dyslipidemias, diabetes, hypertension) and humoral markers of plaque vulnerability (C-reactive protein, interleukin-6, 10 and 18, CD40L) have been identified, a highly sensitive and specific biomarker or protein profile, which could provide information on the stability/vulnerability of atherosclerotic lesions, remains to be identified. In this review, we report several proteomic approaches which have been applied to circulating or resident cells, atherosclerotic plaques or plasma, in the search for new proteins that could be used as cardiovascular biomarkers. First, an example using a differential proteomic approach (2-DE and MS) comparing the secretome from control mammary arteries and atherosclerotic plaques is displayed. Among the different proteins identified, we showed that low levels of HSP-27 could be a potential marker of atherosclerosis. Second, we have revised several studies performed in cells involved in the pathogenesis of atherosclerosis (foam cells and smooth muscle cells). Another approach consists of performing proteomic analysis on circulating cells or plasma, which will provide a global view of the whole body response to atherosclerotic aggression. Circulating cells can bear information reflecting directly an inflammatory or pro-coagulant state related to the pathology. As an illustration, we report that circulating monocytes and plasma in patients with acute coronary syndromes has disclosed that mature Cathepsin D is increased both in the plasma and monocytes of these patients. Finally, the problems of applying proteomic approach directly to plasma will be discussed. The purpose of this review is to provide the reader with an overview of different proteomic approaches that can be used to identify new biomarkers in vascular diseases.

Heat Shock Protein 25-Enriched Plasma Transfusion Preconditions the Heart against Doxorubicin-Induced Dilated Cardiomyopathy in Mice

“…These results imply that the source of the eHsp25 is not the cardiomyocyte and that treatment with eHsp25 can regulate the production of Hsp25 in the heart. How eHsp25/27 could interact with cardiomyocytes or provide cardioprotection in the heart has not been fully elucidated previously, although the plasma level of eHsp27 was studied as a potential marker of atherosclerosis risk in humans (Vivanco et al, 2005;Kardys et al, 2008). Potential correlations between activation of various surface receptors and Dox-induced cardiac injury have been identified (Nozaki et al, 2004).…”

A novel truncated form of apolipoprotein A-I transported by dense LDL is increased in diabetic patients

“…Indeed, it has been suggested previously that cathepsin D could induce hydrolytic modifi cations of LDLs, favoring the formation of foam cells in the intima of human arteries ( 45 ). Moreover, cathepsin D has been shown to be released by atherosclerotic plaques, and increased plasma levels have been found in acute coronary syndrome patients ( 46 ). Although we have found a potential role of cathepsin D in the formation of ApoA-I ⌬ (1-38), we cannot exclude the implication of other enzymes.…”

In Search for Novel Biomarkers of Acute Coronary Syndrome

“…Beside protease function www.intechopen.com and vascular effects, protease detection and quantization in peripheral blood may help detect atheromatous disease stages and aid in clinical decision-making (Vivanco et al, 2005). Patients with coronary artery stenosis have demonstrated increased serum cathepsin L levels than those without lesions detectable by quantitative angiography (Liu et al, 2006a).…”