Regulation of inducible nitric oxide synthase gene expression in vascular smooth muscle cells.
1. Formation of nitric oxide (NO) by the constitutive calcium-dependent NO synthase expressed in endothelial cells plays an important role in the control of local blood flow and vascular homeostasis. Expression of the inducible calcium-independent NO synthase (iNOS) in vascular smooth muscle cells (VSMC), on the other hand, is thought to play a potentially detrimental role in the pathogenesis of chronic inflammation or septic shock. In vascular injury, however, iNOS expression in VSMC may be beneficial as a compensatory mechanism for the lack of endothelial NO synthesis, e.g., by preventing restenosis following angioplasty or heart transplant vasculopathy. 2. Because iNOS activity does not seem to be controlled once the enzyme is expressed, regulation of NO release from iNOS-expressing cells predominantly occurs at the transcriptional and/or posttranscriptional level. 3. This review summarizes what is currently known about the regulation of expression of this enzyme in VSMC, details some of the transcription factors involved therein as well as their mode of activation, and highlights some pharmacological strategies based on these findings that may be employed for the control of iNOS expression in VSMC in the clinical arena.
Hecker
M
M
Department of Cardiovascular Physiology, University of Goettingen, Germany. hecker@veg-physiol.med.uni-goettingen.de
Cattaruzza
M
M
Wagner
A H
AH
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006487:Hemostasis; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D011494:Protein Kinases / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D014158:Transcription, Genetic
D013481:Superoxides; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D011494:Protein Kinases