title: Physiological mechanisms regulating the expression of endothelial-type NO synthase.
abstract: Although endothelial nitric oxide synthase (eNOS) is a constitutively expressed enzyme, its expression is regulated by a number of biophysical, biochemical, and hormonal stimuli, both under physiological conditions and in pathology. This review summarizes the recent findings in this field. Shear stress, growth factors (such as transforming growth factor-beta, fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor), hormones (such as estrogens, insulin, angiotensin II, and endothelin 1), and other compounds (such as lysophosphatidylcholine) upregulate eNOS expression. On the other hand, the cytokine tumor necrosis factor-alpha and bacterial lipopolysaccharide downregulate the expression of this enzyme. The growth status of cells, the actin cytoskeleton, and NO itself are also important regulators of eNOS expression. Both transcriptional and posttranscriptional mechanisms are involved in the expressional regulation of eNOS. Different signaling pathways are involved in the regulation of eNOS promoter activity and eNOS mRNA stability. Changes in eNOS expression and activity under pathophysiological conditions and the pharmacological modulation of eNOS expression are subject of a subsequent brief review (part 2) to be published in the next issue of this journal.
authors.affiliation: Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, Mainz D-55101, Germany.
authors.forename: Huige
authors.initials: H
authors.lastname: Li
authors.forename: Thomas
authors.initials: T
authors.lastname: Wallerath
authors.forename: Ulrich
authors.initials: U
authors.lastname: Förstermann
mesh_terms: D000818:Animals; D001483:Base Sequence; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D011401:Promoter Regions, Genetic / Q000235:genetics; D020871:RNA Stability; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III