Site-Specific Secretome Map Evidences VSMC-Related Markers of Coronary Atherosclerosis Grade and Extent in the Hypercholesterolemic Swine

Disease Markers - Tập 2015 - Trang 1-12 - 2015
Silvia Rocchiccioli1, Antonella Cecchettini2,1, Nadia Ucciferri1, Marianna Terreni1, Federica Viglione1, Maria Giovanna Trivella1, Lorenzo Citti1, Oberdan Parodi1, Gualtiero Pelosi1
1National Research Council, Institute of Clinical Physiology, Via Moruzzi, 56124 Pisa, Italy
2Department of Clinical and Experimental Medicine, University of Pisa, Via Volta, 56126 Pisa, Italy

Tóm tắt

A major drawback in coronary atherosclerosis (ATS) research is the difficulty of investigating early phase of plaque growth and related features in the clinical context. In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent. A wide coronary artery map of secreted proteins has been obtained in high fat (HF) diet induced ATS swine model and a significantly different expression of many proteins related to vascular smooth muscle cell (VSMC) activation/migration has been identified. Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression. A direct correlationR2=0.85was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases. These findings confirmed the pivotal role of VSMCs in coronary plaque development and demonstrated a strong site-specific relation between VSMC-secreted CHI3L1 and lesion grade, suggesting that this protein could be proposed as a useful biomarker for diagnosing and staging of atherosclerotic lesions in coronary artery disease.

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