AMP-activated protein kinase promotes the differentiation of endothelial progenitor cells.
AMP-activated protein kinase promotes the differentiation of endothelial progenitor cells.
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DOI：
10.1161/atvbaha.108.172452
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Li X;Han Y;Pang W;Li C;Xie X;Shyy JY;Zhu Y
内皮祖细胞(EPC)可以分化为内皮细胞(ECs)，并参与出生后的血管生成，但其分化机制尚不清楚。我们研究了AMP激活的蛋白激酶(AMPK)在EPC分化和功能中的作用。血管内皮生长因子导致人脐带血来源的内皮祖细胞中AMPK、乙酰辅酶A羧化酶(ACC)和eNOS的磷酸化。血管内皮细胞标志物VE-cadherin和ICAM-1的表达也被上调，但被AMPK抑制剂化合物C阻断。AMPK激动剂AICAR以时间和剂量依赖的方式增加ACC和eNOS的磷酸化及EC标志物的表达，从而增强AMPK对EPC分化的积极作用。内皮型一氧化氮合酶抑制剂L-NAME可阻断AICAR的作用。在功能上，AICAR增加，而化合物C在体内外抑制EPC的血管生成。此外，洛伐他汀可促进AMPK和eNOS的激活，促进EC标志物的表达，促进EPC的管状形成、黏附和体内血管生成，这一作用可被化合物C阻断。在EPC分化过程中，AMPK激活eNOS为他汀类药物在心血管系统中的多效性作用提供了新的机制。
Endothelial progenitor cells (EPCs) can differentiate into endothelial cells (ECs) and participate in post-natal vasculogenesis, but the mechanism of EPC differentiation remains largely unknown. We investigated the role of AMP-activated protein kinase (AMPK) in EPC differentiation and functions. Vascular endothelial growth factor caused the phosphorylation of AMPK, acetyl-CoA carboxylase (ACC), and eNOS in human cord blood-derived EPCs. The expression of EC markers, including VE-cadherin and ICAM-1, was also increased but blocked by Compound C, an AMPK inhibitor. AICAR, an AMPK agonist, increased the phosphorylation of ACC and eNOS and the expression of EC markers in a time- and dose-dependent manner, which reinforces the positive effect of AMPK on EPC differentiation. The effects of AICAR could be blocked by treatment with L-NAME, an eNOS inhibitor. Functionally, AICAR increased but Compound C decreased the angiogenesis of EPCs in vitro and in vivo. Furthermore, lovastatin promoted the activation of AMPK and eNOS, the expression of EC markers, tube formation, adhesion and in vivo vasculogenesis of EPCs, which could be blocked by treatment with Compound C. The activation of eNOS by AMPK during EPC differentiation provides a novel mechanism for the pleiotropic effects of statins in benefiting the cardiovascular system.