Injury-coupled induction of endothelial eNOS and COX-2 genes: a paradigm for thromboresistant gene therapy.
Nitric oxide (NO) and prostacyclin (PGI2) are potent molecules produced by endothelial cells that act synergistically to maintain normal vascular functions. Recent studies indicate that key enzymes that catalyze the synthesis of these two molecules are induced by chemical and physical factors. Because NO and PGI2 and their synthetic enzymes have short half-lives, transcriptional induction by injurious agents, such as lysophosphatidylcholine (lysoPC), represents an important defense mechanism. LysoPC is capable of inducing constitutive endothelial NO synthase (eNOS) and cyclooxygenase-2 (COX-2), an immediate early gene, with distinct kinetics and possibly distinct transcriptional mechanisms. The importance of injury-coupled eNOS and COX overexpression in vasoprotection is supported by powerful effects of virus-mediated transfer of COX and eNOS genes on defense against thrombosis and intimal hyperplasia in angioplasty-injured carotid arteries in animal models.
Wu
K K
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Division of Hematology, The University of Texas-Houston Health Science Center, Medical School, 77030, USA.
D000818:Animals; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000378:metabolism*; D004790:Enzyme Induction; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008565:Membrane Proteins; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D013927:Thrombosis / Q000517:prevention & control*; D014158:Transcription, Genetic
D007527:Isoenzymes; D008244:Lysophosphatidylcholines; D008565:Membrane Proteins; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases