Abstract 290: Ccr2 Expression Is Increased In Patients With Symptomatic Carotid Arterial Occlusive Disease

Abstract

Objectives: Chemokines and their receptors play critical roles in the progression of atherosclerosis. The chemokine receptor, C-C chemokine receptor type 2 (CCR2), mediates an essential role in the differentiation of pro-inflammatory monocytes into macrophages. Recent studies suggest that proinflamatory macrophages in plaques predict plaque progression. While there is no clinical consensus on which patient with asymptomatic carotid artery stenosis would benefit from carotid endarterectomy (CEA), we hypothesized that CCR2 plaque content may predict plaque progression. Methods: Carotid plaque of ten patients undergoing elective CEA were harvested from the operating room, paraffin-embedded, sectioned into 5μm segments, immuno-stained for CCR2 and CD68, and imaged. Three 200х500μm regions-of-interest (ROIs) were randomly selected within 200μm of the lumen (superficial intima), outside 200μm of the lumen (deep intima), and the arterial media. Two independent observers evaluated the number of CCR2 and/or CD68 positive cells. Counts in each ROI were averaged and analyzed with Student’s t-test. Results: Patients with symptomatic carotid artery stenosis (6/10) demonstrated higher CCR2 and CCR2-CD68 double positive cells within the superficial intima of carotid artery plaques (A, p<0.05, n=10). Similarly, patients with symptomatic disease also showed increased CCR2 in the plaque media (B, p<0.05, n=10). Interestingly, we also observed a higher number of CCR2 positive cells in the media layer of smokers (6/10) compared to non-smokers (C, p<0.05, n=10). Conclusions: Our study demonstrates the close association between CCR2 cellular content and the incidence of symptomatic carotid artery disease. Additionally, CCR2 plaque content appears to correlate with risk-factors such as smoking. These studies have important implications regarding the impact of immune modulation on carotid plaque vulnerability in patients with asymptomatic carotid artery stenosis.