title: Angiopoietin-2 confers Atheroprotection in apoE-/- mice by inhibiting LDL oxidation via nitric oxide.
abstract: Atherosclerosis is promoted by a combination of hypercholesterolemia and vascular inflammation. The function of Angiopoietin (Ang)-2, a key regulator of angiogenesis, in the maintenance of large vessels is unknown. A single systemic administration of Ang-2 adenovirus (AdAng-2) to apoE(-/-) mice fed a Western diet significantly reduced atherosclerotic lesion size ( approximately 40%) and oxidized LDL and macrophage content of the plaques. These beneficial effects were abolished by the inhibition of nitric oxide synthase (NOS). In endothelial cells, endothelial NOS activation per se inhibited LDL oxidation and Ang-2 stimulated NO release in a Tie2-dependent manner to decrease LDL oxidation. These findings demonstrate a novel atheroprotective role for Ang-2 when endothelial cell function is compromised and suggest that growth factors, which stimulate NO release without inducing inflammation, could offer atheroprotection.
authors.affiliation: Institute for Biomedical Research, University of Birmingham, Birmingham, B15 2TT, United Kingdom. a.s.ahmed@bham.ac.uk
authors.forename: Asif
authors.initials: A
authors.lastname: Ahmed
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Niu
authors.forename: Shakil
authors.initials: S
authors.lastname: Ahmad
authors.forename: Bahjat
authors.initials: B
authors.lastname: Al-Ani
authors.forename: Kunal
authors.initials: K
authors.lastname: Chudasama
authors.forename: Allyah
authors.initials: A
authors.lastname: Abbas
authors.forename: Rahul
authors.initials: R
authors.lastname: Potluri
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.forename: Clarence M
authors.initials: CM
authors.lastname: Findley
authors.forename: Gregory K W
authors.initials: GK
authors.lastname: Lam
authors.forename: Jianhua
authors.initials: J
authors.lastname: Huang
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hewett
authors.forename: Melissa
authors.initials: M
authors.lastname: Cudmore
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Kontos
mesh_terms: D000256:Adenoviridae; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics; D010084:Oxidation-Reduction; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic; D014657:Vasculitis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control
chemical_list: D042702:Angiopoietin-2; D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D042787:Receptor, TIE-2