Endothelial prostaglandin and nitric oxide synthesis in atherogenesis and thrombosis.
Human arterial thrombotic disorders are triggered by many agents, with participation of platelets and monocytes, blood coagulation factors and vascular cells. Platelet hyperaggregability appears to be an important risk factor for these disorders. Vascular endothelium possesses several properties to defend against vascular insults and thrombotic atherosclerotic lesions. Two molecules, prostacyclin (PGI2) and nitric oxide (NO), are of particular importance. The rate-limiting step of PGI2 synthesis is cyclooxygenase (COX). Constitutive and upregulated constitutive COX (COX-1) expression and inducible COX (COX-2) expression are important in PGI2 production required for the physiologic and pathologic defense of blood vessels and blood fluidity. NO synthesis is catalyzed by endothelial nitric oxide synthase (eNOS), which can be stimulated by lipid mediators. Virus or non-virus mediated transfer of COX-1 and eNOS are accompanied by augmented PGI2 and NO synthesis, respectively. In animal angioplasty models, it has been shown that transfer of these two genes has a dramatic antithrombotic and anti-intimal hyperplastic effect. Transfers of these two enzymes may have potential therapeutic uses.
Wu
K K
KK
University of Texas-Houston Health Science Center, Vascular Biology Research Center 77030, USA.
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D001792:Blood Platelets / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D013927:Thrombosis / Q000378:metabolism*
D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases