Augmented Expression of Cyclooxygenase-2 in Human Atherosclerotic Lesions

• Published in: The American journal of pathology Vol. 155; no. 4; pp. 1281 - 1291
• Main Authors: Schönbeck, Uwe, Sukhova, Galina K., Graber, Pierre, Coulter, Stephanie, Libby, Peter
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.10.1999; ASIP; American Society for Investigative Pathology
• Subjects: Arteriosclerosis - enzymology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blotting, Western; Cardiology. Vascular system; Cells, Cultured; Cyclooxygenase 1; Cyclooxygenase 2; Endothelium, Vascular - enzymology; Humans; Immunohistochemistry; In Situ Hybridization; Isoenzymes - biosynthesis; Isoenzymes - genetics; Macrophages - enzymology; Medical sciences; Membrane Proteins; Microcirculation - enzymology; Muscle, Smooth, Vascular - enzymology; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandin-Endoperoxide Synthases - genetics; Regular; RNA, Messenger - biosynthesis; Human; Immunohistochemistry; Cell culture; Prostaglandin-endoperoxide synthase; Biochemical analysis; Enzyme; Pathogenesis; In situ; Cardiovascular disease; Inflammation; Hybridization; In vitro; Vascular disease; Pathology; Atherosclerosis; Oxidoreductases; Molecular biology
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)65230-3

Cyclooxygenase-1 (Cox-1) and Cox-2 convert arachidonic acid to prostaglandin H 2, the precursor of other prostaglandins and thromboxanes, eicosanoids important in vascular pathophysiology. However, knowledge of the expression of cyclooxygenases within atherosclerotic lesions is scant. This study tested the hypothesis that human atheroma and nonatherosclerotic arteries express the two Cox isoforms differentially. Cox-1 mRNA and protein localized on endothelial and medial smooth muscle cells of normal arteries ( n = 5), whereas Cox-2 expression was not detectable. In contrast, atheromatous ( n = 7) lesions contained both Cox-1 and Cox-2, colocalizing mainly with macrophages of the shoulder region and lipid core periphery, whereas smooth muscle cells showed lower levels, as demonstrated by immunohistochemical and in situ hybridization analysis. Furthermore, microvascular endothelium in plaques showed notable staining for both isoforms. In accord with immunohistochemical studies, Western blot analysis of protein extracts from normal arteries revealed constitutive Cox-1, but not Cox-2, expression. Extracts of atheromatous lesions, however, contained both Cox-1 and Cox-2 protein, detected as two immunoreactive proteins of approximately 70 and 50 kd. Macrophages expressed the short form of Cox-1/-2 constitutively after several days of in vitro culture, rather than the 70-kd protein. These results shed new light on the inflammatory pathways that operate in human atheroma. In particular, the expression of Cox-2 in atheromatous, but not in unaffected, arteries has therapeutic implications, given the advent of selective Cox-2 inhibitors.