Prostacyclin and nitric oxide-related gene transfer in preventing arterial thrombosis and restenosis.
Prostacyclin (PGI2) and nitric oxide (NO) are potent vascular mediators, playing key roles in protecting arterial wall from injury-induced lesions. The key enzyme that catalyzes PGI2 biosynthesis is cyclooxygenase (COX). COX-1 undergoes auto-inactivation, which severely limits PGI2 synthesis. Overexpression of COX-1 in cultured endothelial cells by COX-1 gene transfer was accompanied by a higher capacity for and sustained synthesis of PGI2. Adenovirus-mediated COX-1 gene transfer to angioplasty damaged carotid arteries in pigs augmented PGI2 synthesis and prevents thrombus formation. Transfer of endothelial NO synthase (eNOS) into angioplasty injured, carotid arteries was reported to suppress intimal hyperplasia in rats. Transfer of PGI2 and NO synthetic enzymes restores the vasoprotective properties and represents an exciting new strategy for treating arterial thrombotic disorders.
Wu
K K
KK
University of Texas-Houston Medical School, Vascular Biology Research Center 77030, USA.
D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D011464:Epoprostenol / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D051381:Rats; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
D007527:Isoenzymes; D008565:Membrane Proteins; D009569:Nitric Oxide; D011464:Epoprostenol; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat