Endothelium-derived microparticles inhibit angiogenesis in the heart and enhance the inhibitory effects of hypercholesterolemia on angiogenesis

被引：55
作者：
Ou, Zhi-Jun [2 ,3 ]
Chang, Feng-Jun [1 ,3 ]
Luo, Dan [1 ,3 ]
Liao, Xiao-Long [1 ,3 ]
Wang, Zhi-Ping [1 ,3 ]
Zhang, Xi [1 ,3 ]
Xu, Ying-Qi [1 ,3 ]
Ou, Jing-Song [1 ,3 ]
机构：
[1] Sun Yat Sen Univ, Div Cardiac Surg, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 1, Div Hypertens & Vasc Dis, Guangzhou 510080, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 1, Key Lab Assisted Circulat, Minist Hlth, Guangzhou 510080, Guangdong, Peoples R China
来源：
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2011年 / 300卷 / 04期
基金：
中国国家自然科学基金;
关键词：
cardiovascular diseases; endothelial nitric oxide synthase; nitric oxide; NITRIC-OXIDE SYNTHASE; CORONARY-ARTERY-DISEASE; SHED MEMBRANE MICROPARTICLES; V+ APOPTOTIC MICROPARTICLES; TYPE-2; DIABETES-MELLITUS; GROWTH-FACTOR; HYPERTENSIVE PATIENTS; IN-VITRO; FAMILIAL HYPERCHOLESTEROLEMIA; OXIDATIVE STRESS;
D O I：
10.1152/ajpendo.00611.2010
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Ou ZJ, Chang FJ, Luo D, Liao XL, Wang ZP, Zhang X, Xu YQ, Ou JS. Endothelium-derived microparticles inhibit angiogenesis in the heart and enhance the inhibitory effects of hypercholesterolemia on angiogenesis. Am J Physiol Endocrinol Metab 300: E661-E668, 2011. First published January 18, 2011; doi: 10.1152/ajpendo. 00611.2010.-Therapeutic angiogenesis remains unsuccessful in coronary artery disease. It is known that plasma endothelium-derived microparticles (EMPs) are increased in coronary artery disease and that hypercholesterolemia can inhibit angiogenesis. We evaluated the relationship between EMPs and hypercholesterolemia in the impairment of angiogenesis. EMPs isolated from human umbilical vein endothelial cells were injected into low-density lipoprotein receptor-null (LDLr-/-) mice fed a Western diet for 2 wk and C57BL6 mice for 6 h or were directly added to the tissue culture media. Hearts isolated from mice were sectioned and cultured, and endothelial tube formation was measured. The expression and phosphorylation of endothelial NO synthase (eNOS) and the generation of NO in the hearts were determined. Angiogenesis was inhibited by pathophysiological concentrations of EMPs but not physiological concentrations of EMPs in hearts from C57BL6 mice. However, angiogenesis was inhibited by EMPs at both physiological and pathophysiological concentrations of EMPs in hearts from hypercholesterolemic LDLr-/- mice. Pathophysiological concentrations of EMPs decreased eNOS phosphorylation at Ser(1177) and NO generation without altering eNOS expression in hearts from C57BL6 mice. Both physiological and pathophysiological concentrations of EMPs decreased not only eNOS phosphorylation at Ser(1177) and NO generation, but eNOS expression in hypercholesterolemic hearts from LDLr-/- mice. These data demonstrated that pathophysiological concentrations of EMPs could inhibit angiogenesis in hearts by decreasing eNOS activity. EMPs and hypercholesterolemia mutually enhanced their inhibitory effect of angiogenesis by inducing eNOS dysfunction. Our findings suggest a novel mechanism by which hypercholesterolemia impairs angiogenesis.
引用
收藏
页码：E661 / E668
页数：8
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