Tissue expression of functional and silent receptors of CCL2 (Chemokine (C-C motif) ligand 2) in coronary arteries: a necropsy study

Identifier:  TFG:114

Handle: https://hdl.handle.net/20.500.11797/TFG114

Authors:  Cabré Casares, Noemí

Abstract:
BACKGROUND: Atherosclerosis (and its manifestation in coronary arteries) is a chronic disease that remains as one of the leading cause of morbidity and mortality worldwide. It is considered a chronic inflammatory disease mainly mediated by chemokines. Chemokines, especially CCL2, play a critical role in the migration of inflammatory cells. CCL2 (chemokine (C-C motif) ligand 2) is a monocyte chemoattractant protein that has an important role in the progression of atherosclerotic plaque. The biological function of CCL2 is possible by its union to CCR2 receptor, but its chemotactic function can be attenuated by “silent” or atypical receptors (DARC and D6). They regulate CCL2 levels in order to balance the inflammatory process. OBJECTIVE: This study aimed to characterize and compare coronary arteries from individuals that died due to cardiovascular reasons (coronary artery disease, CAD) and the same type of arteries from patients that died from other reasons (unaffected individuals) in order to understand the interactions between CCL2 and its receptors in the development of atherosclerosis. Moreover, the trial aimed to propose a biomarker able to distinguish between affected and non-affected individuals METHODS: We evaluated the histological changes between the arteries in both groups. We also examined the localization and the expression of different proteins (CCL2, CCR2, DARC, D6 and CD68) in a total 87 subjects, including 19 non-affected patients and 68 patients with CAD by immunochemical staining analysis. RESULTS: There was a significant increase in the expression of CCL2, CCR2, CD68, D6 and DARC in subjects with CAD compared to the non-affected individuals. Results obtained indicate a significative association between CCL2 and progression of atherosclerosis in patients with CAD. CONCLUSIONS: The presence of CCL2 and its receptors are a key factor in the initiation and progression of atherosclerosis and CCL2 has been proposed as an attractive biomarker for coronary artery disease.