Several studies have evidenced variations in plasma glycosaminoglycans content in physiological and pathological conditions. In normal human plasma GAGs are present mainly as undersulfated chondroitin sulfate (CS). The aim of the present study was to evaluate possible correlations between plasma CS level/structure and the presence/typology of carotid atherosclerotic lesion. Plasma CS was purified from 46 control subjects and 47 patients undergoing carotid endarterectomy showing either a soft or a hard plaque. The concentration and structural characteristics of plasma CS were assessed by capillary electrophoresis of constituent unsaturated fluorophore-labeled disaccharides. Results showed that the concentration of total CS isomers was increased by 21.4% ( ) in plasma of patients, due to a significant increase of undersulfated CS. Consequently, in patients the plasma CS charge density was significantly reduced with respect to that of controls. After sorting for plaque typology, we found that patients with soft plaques and those with hard ones differently contribute to the observed changes. In plasma from patients with soft plaques, the increase in CS content was not associated with modifications of its sulfation pattern. On the contrary, the presence of hard plaques was associated with CS sulfation pattern modifications in presence of quite normal total CS isomers levels. These results suggest that the plasma CS content and structure could be related to the presence and the typology of atherosclerotic plaque and could provide a useful diagnostic tool, as well as information on the molecular mechanisms responsible for plaque instability. 1. Introduction Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in medium and large arteries. Plaque rupture and thrombosis are the most important clinical complication in the pathogenesis of acute coronary syndromes and peripheral vascular disease [1, 2]. Although numerous risk factors such as hypertension, diabetes, and hyperlipidemia are thought to play a role in the development and progression of this pathology [3], the mechanisms underlying plaque formation and progression are still largely unknown. Abnormal expression and structural modifications of arterial chondroitin sulfate proteoglycans (CS-PGs) have been implicated in atherosclerosis progression [4–6]. Arterial CS-PGs are markedly increased in early atherosclerotic lesions, participating in lipid retention, modification, and accumulation. Furthermore, CS-PGs play a key role in inflammation processes
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