Globular adiponectin improves high glucose-suppressed endothelial progenitor cell function through endothelial nitric oxide synthase dependent mechanisms

被引：65

作者：

Huang, Po-Hsun ^{[2
,4
,5
]}

Chen, Jia-Shiong ^{[8
]}

Tsai, Hsiao-Ya ^{[4
]}

Chen, Yung-Hsiang ^{[6
]}

Lin, Feng-Yen ^{[7
]}

Leu, Hsin-Bang ^{[2
,3
,4
,5
]}

Wu, Tao-Cheng ^{[2
,5
]}

Lin, Shing-Jong ^{[1
,2
,4
,5
]}

Chen, Jaw-Wen ^{[1
,2
,5
,8
]}

机构：

[1] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei, Taiwan

[2] Taipei Vet Gen Hosp, Div Cardiol, Dept Internal Med, Taipei, Taiwan

[3] Taipei Vet Gen Hosp, Healthcare & Management Ctr, Taipei, Taiwan

[4] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan

[5] Natl Yang Ming Univ, Cardiovasc Res Ctr, Taipei 112, Taiwan

[6] China Med Univ, Grad Inst Integrated Med, Coll Chinese Med, Taichung, Taiwan

[7] Taipei Med Univ & Hosp, Div Internal Med, Taipei, Taiwan

[8] Natl Yang Ming Univ, Inst & Dept Pharmacol, Taipei 112, Taiwan

来源：

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY | 2011年 / 51卷 / 01期

关键词：

Adiponectin; Endothelial progenitor cell; Nitric oxide; Mitogen-activated protein kinase; Hyperglycemia; ACTIVATED PROTEIN-KINASE; VASCULAR COMPLICATIONS; PLASMA-PROTEIN; ADIPOSE-TISSUE; DYSFUNCTION; REENDOTHELIALIZATION; HYPOADIPONECTINEMIA; ASSOCIATION; INVOLVEMENT; ADHESION;

D O I：

10.1016/j.yjmcc.2011.03.008

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Plasma levels of adiponectin, an adipose-specific protein with putative anti-atherogenic properties, could be down-regulated in obese and diabetic subjects. Recent insights suggest that the injured endothelial monolayer is regenerated by circulating endothelial progenitor cells (EPCs), but high glucose reduces number and functions of EPCs. Here, we tested the hypothesis that globular adiponectin can improve high glucosesuppressed EPC functions by restoration of endothelial nitric oxide synthase (eNOS) activity. Late EPCs isolated from healthy subjects appeared with cobblestone shape at 2-4 weeks. EPCs were incubated with high glucose (25 mM) and treatment with globular adiponectin for functional study. Migration and tube formation assays were used to evaluate the vasculogenetic capacity of EPCs. The activities of eNOS, Akt and concentrations of nitric oxide (NO) were also determined. Administration of globular adiponectin at physiological concentrations promoted EPC migration and tube formation, and dose-dependently upregulated phosphorylation of eNOS. Akt and augmented NO production. Chronic incubation of EPCs in high-glucose medium significantly impaired EPC function and induced cellular senescence, but these suppression effects were reversed by treatment with globular adiponectin. Globular adiponectin reversed high glucose-impaired EPC functions through NO- and p38 MAPK-related mechanisms. In addition, nude mice that received EPCs treated with adiponectin in high glucose medium showed a significant improvement in blood now than those received normal saline and EPCs incubated in high glucose conditions. The administration of globular adiponectin improved high glucose-impaired EPC functions in vasculogenesis by restoration of eNOS activity. These beneficial effects may provide some novel rational to the vascular protective properties of adiponectin. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：109 / 119

页数：11

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