Coexpression of cyclooxygenase-2 and matrix metalloproteinases in human aortic atherosclerotic lesions

Inflammation appears to have a major role in the development of atheroscler osis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the productio n of matrix metalloproteinases (MMPs). This study aimed to investigate athe rosclerosis in human aortas for in situ tissue distribution of COX-2, MMPs including MMP-9 and membrane type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemical studies were performed on atherosclerotic lesions of aortas from patients with aortic aneurysms (n=4 ) and dissections (n=3) by using antibodies to COX-2, MMP-9, MT1-MMP, and T IMP-2. Control tissues were obtained from traumatically dissected aortas (n =2). All specimens from diseased aortas had atherosclerotic lesions ranging from fatty streak to atheromatous plaques. In control, there was no expres sion of COX-2, MMP-9, sind MT1-MMP in all aortic layers. Immunoreactivity f or COX-2 was predominantly noted in macrophages and smooch muscle cells (SM Cs) of the intima including atherosclerotic plaque itself and the medial la yer of the plaque base, as well as in SMCs and endothelial lining of the va sa vasorum in the adventitia. Immunoreactivity for MMP-9 and MT1-MMP was fo und in the same distribution as that of COX-2. Additionally, the expression of TIMP-2 increased in relation to MMP-9 expression. This study demonstrat es that COX-2 is coexpressed with MMP-9 and MT1-MMP, not only by macrophage s and SMCs in atherosclerotic lesions, but also in endothelial lining of th e vase vasorum of human aortas. Thus, vascular inflammatory reactions may i nfluence extracellular matrix remodeling by coactivation of MMPs in the dev elopment of atherosclerosis and, in turn, the progression of disease.