title: Endothelial arginase II: a novel target for the treatment of atherosclerosis.
abstract: Oxidized low-density lipoproteins increase arginase activity and reciprocally decrease endothelial NO in human aortic endothelial cells. Here, we demonstrate that vascular endothelial arginase activity is increased in atherogenic-prone apolipoprotein E-null (ApoE(-/-)) and wild-type mice fed a high cholesterol diet. In ApoE(-/-) mice, selective arginase II inhibition or deletion of the arginase II gene (Arg II(-/-) mice) prevents high-cholesterol diet-dependent decreases in vascular NO production, decreases endothelial reactive oxygen species production, restores endothelial function, and prevents oxidized low-density lipoprotein-dependent increases in vascular stiffness. Furthermore, arginase inhibition significantly decreases plaque burden. These data indicate that arginase II plays a critical role in the pathophysiology of cholesterol-mediated endothelial dysfunction and represents a novel target for therapy in atherosclerosis.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, the Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Ryoo
authors.forename: Gaurav
authors.initials: G
authors.lastname: Gupta
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benjo
authors.forename: Hyun Kyo
authors.initials: HK
authors.lastname: Lim
authors.forename: Andre
authors.initials: A
authors.lastname: Camara
authors.forename: Gautam
authors.initials: G
authors.lastname: Sikka
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Lim
authors.forename: Jayson
authors.initials: J
authors.lastname: Sohi
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Santhanam
authors.forename: Kevin
authors.initials: K
authors.lastname: Soucy
authors.forename: Eric
authors.initials: E
authors.lastname: Tuday
authors.forename: Ezra
authors.initials: E
authors.lastname: Baraban
authors.forename: Monica
authors.initials: M
authors.lastname: Ilies
authors.forename: Gary
authors.initials: G
authors.lastname: Gerstenblith
authors.forename: Daniel
authors.initials: D
authors.lastname: Nyhan
authors.forename: Artin
authors.initials: A
authors.lastname: Shoukas
authors.forename: David W
authors.initials: DW
authors.lastname: Christianson
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Alp
authors.forename: Hunter C
authors.initials: HC
authors.lastname: Champion
authors.forename: David
authors.initials: D
authors.lastname: Huso
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D001119:Arginase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology; D002784:Cholesterol / Q000008:administration & dosage; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D015854:Up-Regulation; D014655:Vascular Resistance
chemical_list: D001057:Apolipoproteins E; D009569:Nitric Oxide; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III; C481673:Arg2 protein, mouse; D001119:Arginase