Overexpression of Toll‐like receptor‐2 in human carotid artery plaques reflects clinical severity of atherosclerosis

Abstract

Toll‐like receptors (TLR) and cyclooxygenases (COX) are increasingly implicated in the pathogenesis of atherosclerosis. In this study, carotid endarterectomy plaques collected during surgery from nine patients with significant occlusive disease were quantitatively analyzed for the expression of TLR2, TLR4, COX1 and COX2 by qRT‐PCR, and for the presence of mast cells, T‐lymphocytes and macrophages by immunohistochemistry. Atherosclerotic plaques predominantly occurred at the carotid bifurcation, and had a 2–16 fold higher expression of TLR2 mRNA compared to the shoulder area. Localized plaques occurring away from the carotid bifurcation were predominantly fibrotic and had the lowest levels of TLR2 expression. The gene expression and inflammatory profile of each specimen were subsequently compared with the corresponding patient's clinical severity of atherosclerotic disease. The patient with the highest expression of TLR2 in the plaque also had the highest levels of TLR4 and COX2 mRNA, and the highest number of T‐lymphocytes and macrophages. This patient developed atherosclerotic disease at an earlier age with severe involvement of carotid, coronary and peripheral arteries, and had significant cutaneous S. aureus infections. These results suggest that the magnitude of TLR2 expression in the plaque has a direct association with the severity of widespread atherosclerotic disease. (Supported by NIH R01‐ HL070101 and 3R01‐HL070101–04S1, the Carey Arthritis Fund, the Audrey E Smith Fund, and the Dept. of Medicine Research Office, University of Kansas Med Ctr.)