ENDOTHELIAL PROSTAGLANDIN AND NITRIC-OXIDE SYNTHESIS IN ATHEROGENESISAND THROMBOSIS

Human arterial thrombotic disorders are triggered by many agents, with participation of platelets and monocytes, blood coagulation factors a nd vascular cells. Platelet hyperaggregability appears to be an import ant risk factor for these disorders. Vascular endothelium possesses se veral properties to defend against vascular insults and thrombotic ath erosclerotic lesions. Two molecules, prostacyclin (PGI(2)) and nitric oxide (NO), are of particular importance. The rate-limiting step of PG I(2) synthesis is cyclooxygenase (COX). Constitutive and upregulated c onstitutive COX (COX-1) expression and inducible COX (COX-2) expressio n are important in PGI(2) production required for the physiologic and pathologic defense of blood vessels and blood fluidity. NO synthesis i s catalyzed by endothelial nitric oxide synthase (eNOS), which call be stimulated by lipid mediators. Virus or non-virus mediated transfer o f COX-1 and eNOS are accompanied by augmented PGI(2) and NO synthesis, respectively. In animal angioplasty models, it has been shown that tr ansfer of these two genes has a dramatic antithrombotic and anti-intim al hyperplastic effect. Transfers of those two enzymes may have potent ial therapeutic uses.