Angiopoietin-2 Confers Atheroprotection in apoE-/- Mice by Inhibiting LDL Oxidation via Nitric Oxide

被引：44

作者：

Ahmed, Asif ^{[1
]}

Fujisawa, Takeshi ^{[1
]}

Niu, Xi-Lin ^{[2
]}

Ahmad, Shakil ^{[1
]}

Al-Ani, Bahjat ^{[1
]}

Chudasama, Kunal ^{[1
]}

Abbas, Allyah ^{[1
]}

Potluri, Rahul ^{[1
]}

Bhandari, Vineet ^{[3
]}

Findley, Clarence M. ^{[2
]}

Lam, Gregory K. W. ^{[2
]}

Huang, Jianhua ^{[2
]}

Hewett, Peter W. ^{[1
]}

Cudmore, Melissa ^{[1
]}

Kontos, Christopher D. ^{[2
]}

机构：

[1] Univ Birmingham, Inst Biomed Res, Birmingham B15 2TT, W Midlands, England

[2] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA

[3] Yale Univ, Dept Pediat, New Haven, CT 06520 USA

来源：

CIRCULATION RESEARCH | 2009年 / 104卷 / 12期

基金：

英国医学研究理事会;

关键词：

angiopoietin-2; atherosclerosis; endothelial cells; LDL cholesterol; nitric oxide; nitric oxide synthases; LOW-DENSITY-LIPOPROTEIN; ENDOTHELIAL-CELLS; SIGNAL-TRANSDUCTION; GENE-TRANSFER; SYNTHASE; GROWTH; ANGIOGENESIS; DYSFUNCTION; RECEPTOR; ACTIVATION;

D O I：

10.1161/CIRCRESAHA.109.196154

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (approximate to 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.

引用

页码：1333 / U33

页数：21

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