Abstract

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 correlation (R 2 = 0.85) was 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.

Highlights

  • Coronary atherosclerosis (ATS) is the underlying pathology of major acute events associated with thrombotic obstruction of vessel lumen and a leading cause of morbidity and mortality in Western countries [1, 2].Identification of molecular factors associated with coronary atherogenesis has relevant implications for diagnosis, prevention, and treatment of overt coronary artery disease (CAD), especially when significant associations emerge between these factors and the ATS grade, lesion extent, and progression.Within this context, proteome profiling represents an interesting approach to disclose a broad spectrum of cellular proteins and peptides and to propose putative biomarkers [3]

  • Animals were allocated into two groups: controls fed on standard chow (CTRL, n = 6) and animals fed on high fat cholesterol-enriched diet (HF, n = 6) for 4 months (119 days)

  • The plasma lipid profile was evaluated: plasma triglycerides (TGs), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC) content were measured by enzymatic colorimetric reactions using commercial kits (Synchron CX9 Pro, Beckman Coulter Inc., USA)

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Summary

Introduction

Identification of molecular factors associated with coronary atherogenesis (i.e., coronary plaque formation and early progression) has relevant implications for diagnosis, prevention, and treatment of overt coronary artery disease (CAD), especially when significant associations emerge between these factors and the ATS grade, lesion extent, and progression. Within this context, proteome profiling represents an interesting approach to disclose a broad spectrum of cellular proteins and peptides and to propose putative biomarkers [3]. In order to reduce sample complexity in proteome studies and to obtain human tissue representatives of the early stages of plaque formation and progression, de la Cuesta et al have recently [5] analyzed the medial layer of atherosclerotic coronary arteries by 2D-DIGE, highlighting a differential

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