Heme oxygenase 1 is differentially involved in blood flow-dependent arterial remodeling: role of inflammation, oxidative stress, and nitric oxide

TitreHeme oxygenase 1 is differentially involved in blood flow-dependent arterial remodeling: role of inflammation, oxidative stress, and nitric oxide
Type de publicationArticle de revue
AuteurFreidja, M. L, Toutain, Bertrand, Caillon, Antoine, Desquiret-Dumas, Valérie , Lambert, Diane, Loufrani, Laurent , Procaccio, Vincent , Henrion, Daniel
EditeurAmerican Heart Association
TypeArticle scientifique dans une revue à comité de lecture
Année2011
LangueAnglais
Date2011
Numéro2
Pagination225 - 31
Volume58
Titre de la revueHypertension
ISSN1524-4563
Mots-clésAcetophenones/pharmacology, Animals, Endothelium, Vascular/drug effects/metabolism, Heme Oxygenase-1/metabolism, Hemodynamics/drug effects, Inflammation/metabolism, Macrophages/drug effects/metabolism, Mesenteric Arteries/drug effects/metabolism, Metalloporphyrins/pharmacology, Mice, Mice, Knockout, Nitric Oxide Synthase Type III/genetics/metabolism, Nitric Oxide/metabolism, Oxidative Stress/drug effects/physiology, Protoporphyrins/pharmacology, Rats, Rats, Wistar, Regional Blood Flow/drug effects/physiology, Vascular Resistance/drug effects, Vasodilation/drug effects
Résumé en anglais

Heme oxygenase 1 is induced by hemodynamic forces in vascular smooth muscle and endothelial cells. We investigated the involvement of heme oxygenase 1 in flow (shear stress)-dependent remodeling. Two or 14 days after ligation of mesenteric resistance arteries, vessels were isolated. In rats, at 14 days, diameter increased by 23% in high-flow arteries and decreased by 22% in low-flow arteries compared with normal flow vessels. Heme oxygenase activity inhibition using Tin-protoporphyrin abolished diameter enlargement in high-flow arteries and accentuated arterial narrowing in low-flow arteries (32% diameter decrease versus 22% in control). Two days after ligation, heme oxygenase 1 expression increased in high-flow and low-flow vessels, in association with a reduced mitochondrial aconitase activity (marker of oxidative stress) in high-flow arteries only. Inhibition of macrophage infiltration (clodronate) decreased heme oxygenase 1 induction in low-flow but not in high-flow arteries. Similarly, inhibition of NADPH oxidase activity (apocynin) decreased heme oxygenase 1 induction in low-flow but not high-flow arteries. However, dihydroethidium staining was higher in high-flow and low-flow compared with normal flow arteries. In arteries cannulated in an arteriograph, heme oxygenase 1 mRNA increased in a flow-dependent manner and was abolished by N(G)-nitro-l-arginine methyl ester, catalase, or mitochondrial electron transport chain inhibition. Furthermore, heme oxygenase 1 induction using cobalt-protoporphyrin restored altered high-flow remodeling in endothelial NO synthase knockout mice. Thus, in high-flow remodeling, heme oxygenase 1 induction depends on shear stress-generated NO and mitochondria-derived hydrogen peroxide. In low-flow remodeling, heme oxygenase 1 induction requires macrophage infiltration and is mediated by NADPH oxidase-derived superoxide.

URL de la noticehttp://okina.univ-angers.fr/publications/ua8264
DOI10.1161/HYPERTENSIONAHA.111.170266
Lien vers le document

http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.170266

Titre abrégéHypertension