Angiopoietin-2 confers Atheroprotection in apoE-/- mice by inhibiting LDL oxidation via nitric oxide.
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.
Ahmed
Asif
A
Institute for Biomedical Research, University of Birmingham, Birmingham, B15 2TT, United Kingdom. a.s.ahmed@bham.ac.uk
Fujisawa
Takeshi
T
Niu
Xi-Lin
XL
Ahmad
Shakil
S
Al-Ani
Bahjat
B
Chudasama
Kunal
K
Abbas
Allyah
A
Potluri
Rahul
R
Bhandari
Vineet
V
Findley
Clarence M
CM
Lam
Gregory K W
GK
Huang
Jianhua
J
Hewett
Peter W
PW
Cudmore
Melissa
M
Kontos
Christopher D
CD
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
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