Globular adiponectin improves high glucose-suppressed endothelial progenitor cell function through endothelial nitric oxide synthase dependent mechanisms
Globular adiponectin improves high glucose-suppressed endothelial progenitor cell function through endothelial nitric oxide synthase dependent mechanisms
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DOI：
10.1016/j.yjmcc.2011.03.008
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发表时间：
2011-07-01
影响因子：
5
通讯作者：
Chen, Jaw-Wen
中科院分区：
文献类型：
--
作者：
Huang, Po-Hsun;Chen, Jia-Shiong;Chen, Jaw-Wen
脂联素是一种脂肪特异性蛋白质，具有抗动脉粥样硬化的作用，其血浆水平在肥胖和糖尿病患者中下调。最近的见解表明，损伤的内皮单层是由循环内皮祖细胞（EPCs）再生的，但高糖降低了EPCs的数量和功能。在此，我们验证了球状脂联素可以通过恢复内皮型一氧化氮合酶（eNOS）活性来改善高糖抑制的EPC功能的假设。从健康受试者中分离的晚期EPCs在2-4周时出现鹅卵石形状。将EPCs与高葡萄糖（25 mM）孵育并用球状脂联素处理用于功能研究。迁移和管形成实验用于评估EPCs的血管生成能力。同时测定内皮型一氧化氮合酶（eNOS）、Akt活性及一氧化氮（NO）含量。在生理浓度的球状脂联素的管理促进EPC迁移和管的形成，并剂量依赖性上调eNOS的磷酸化。Akt和增强的NO产生。长期孵育的EPCs在高糖培养基中显着损害EPC功能和诱导细胞衰老，但这些抑制作用被逆转的治疗与球状脂联素。球状脂联素通过NO和p38 MAPK相关机制逆转高糖损伤的EPC功能此外，在高糖培养基中接受脂联素处理的EPCs的裸鼠，现在比接受生理盐水和高糖条件下孵育的EPCs的裸鼠显示出显著的血液改善。球状脂联素通过恢复eNOS活性改善高糖损伤的EPC在血管发生中的功能。这些有益作用可能为脂联素的血管保护作用提供了新的理论依据。(C)2011爱思唯尔有限公司版权所有。
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.