Augmented expression of cyclooxygenase-2 in human atherosclerotic lesions

Cyclooxygenase-1 (Cox-1) and Cox-2 convert arachidonic acid to prostaglandi n 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 tes ted the hypothesis that human atheroma and nonatherosclerotic arteries expr ess the two Cox isoforms differentially, Cox-1 mRNA and protein localized o n endothelial and medial smooth muscle cells of normal arteries (n = 5), wh ereas Cox-2 expression was not detectable. In contrast, atheromatous (n = 7 ) lesions contained both Cox-1 and Cox-2, colocalizing mainly with macropha ges of the shoulder region and Lipid core periphery, whereas smooth muscle cells showed lower levels, as demonstrated by immunohistochemical and ill s itu hybridization analysis. Furthermore, microvascular endothelium in plaqu es showed notable staining for both isoforms, In accord with immunohistoche mical studies, Western blot analysis of protein extracts from normal arteri es revealed constitutive Cox-1, but not Cox-2, expression. Extracts of athe romatous 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 i n vitro culture, rather than the 70-kd protein. These results shed new ligh t on the inflammatory pathways that operate in human atheroma. In particula r, the expression of Cox-2 in atheromatous, but not in unaffected, arteries has therapeutic implications, given the advent of selective Cox-2 inhibito rs.