Nitric oxide (NO) is intimately involved in vascular homeostasis through its antiplatelet, antiproliferative, and vasodilating actions. Because of these beneficial properties, methods of harnessing NO for the prevention of vascular injury responses, such as intimal hyperplasia, are being explored. One such method involves gene transfer of an NO synthase (NOS) to sites of vascular injury to provide for local NO synthesis. Gene delivery of the inducible NOS (iNOS) cDNA to sites of vascular injury in animal models dramatically reduced smooth muscle proliferation and intimal hyperplasia. The cellular mechanisms by which NO inhibits smooth muscle cell proliferation appear to be independent of cyclic guanosine monophosphate production but are linked to the upregulation of the cell cycle inhibitor p21. p21 upregulation occurs independent of p53 expression. Instead, p42/44 mitogen activated protein kinase activation by NO results in reduced cellular proliferation and increased p21 expression, suggesting NO inhibits intimal hyperplasia through cell cycle arrest as mediated by p21 and the signaling pathway involved in p21 upregulation may be regulated by p42/44 mitogen activated protein kinase. Copyright (C) 2000 by W.B. Saunders Company.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Obstetrics and Gynecology