title: ET-1 and NOS III gene expression regulation by plaque-free and plaque-prone hemodynamic conditions.
abstract: Both plaque-free and plaque-prone hemodynamic environments induce an increase in the oxidative state of endothelial cells (ECs), whereas differential gene expression regulation was described in cells exposed to these conditions. In order to investigate the role of the increased oxidative state in flow-regulation of gene expression, we first exposed EC to non-pulsed unidirectional shear stress. These conditions only slightly increases ECs oxidative state and endothelin-1 (ET-1) mRNA expression, whereas endothelial nitric oxide synthase (NOS III) mRNA level were significantly up-regulated. On the contrary, both ET-1 and NOS III gene expression were significantly induced in EC exposed to pulsed-unidirectional flow (plaque-free). Only ET-1 gene expression was up-regulated by oscillatory flow (plaque-prone). Moreover, use of an antioxidant only partially inhibited NOS III gene up-regulation by unidirectional flow, whereas it completely abrogated ET-1 gene up-regulation by unidirectional and oscillatory flows. Thus suggesting that mechanical forces regulate gene expression in ECs both via oxidative stress-dependent and -independent mechanisms.
authors.affiliation: Division of Hypertension and Vascular Medicine, CHUV, 1011 Lausanne, Switzerland.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Mattart
authors.forename: Lucia
authors.initials: L
authors.lastname: Mazzolai
authors.forename: Céline
authors.initials: C
authors.lastname: Chambaz
authors.forename: Daniel
authors.initials: D
authors.lastname: Hayoz
authors.forename: Hans R
authors.initials: HR
authors.lastname: Brunner
authors.forename: Paolo
authors.initials: P
authors.lastname: Silacci
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics; D018056:Hemorheology; D040542:Mechanotransduction, Cellular / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D010084:Oxidation-Reduction; D011673:Pulsatile Flow / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D013314:Stress, Mechanical
chemical_list: D000975:Antioxidants; D019332:Endothelin-1; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase