Angiogenic Dysfunction in Bone Marrow-Derived Early Outgrowth Cells from Diabetic Animals Is Attenuated by SIRT1 Activation

被引：18

作者：

Yuen, Darren A. ^{[1
]}

Zhang, Yanling ^{[1
]}

Thai, Kerri ^{[1
]}

Spring, Christopher ^{[1
]}

Chan, Lauren ^{[1
]}

Guo, Xiaoxin ^{[2
]}

Advani, Andrew ^{[1
]}

Sivak, Jeremy M. ^{[2
]}

Gilbert, Richard E. ^{[1
]}

机构：

[1] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Dept Med, Toronto, ON M5B 1T8, Canada

[2] Univ Toronto, Div Visual Sci, Toronto Western Res Inst, Univ Hlth Network, Toronto, ON, Canada

来源：

STEM CELLS TRANSLATIONAL MEDICINE | 2012年 / 1卷 / 12期

基金：

加拿大健康研究院;

关键词：

Diabetes; Angiogenesis; Early outgrowth cell; SIRT1; Chemokine; ENDOTHELIAL PROGENITOR CELLS; VASCULAR COMPLICATIONS; RENAL INJURY; TRANSPLANTATION; STRATEGY; GROWTH; MODEL;

D O I：

10.5966/sctm.2012-0026

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Impaired endothelial repair is a key contributor to microvascular rarefaction and consequent end-organ dysfunction in diabetes. Recent studies suggest an important role for bone marrow-derived early outgrowth cells (EOCs) in mediating endothelial repair, but the function of these cells is impaired in diabetes, as in advanced age. We sought to determine whether diabetes-associated EOC dysfunction might be attenuated by pharmacological activation of silent information regulator protein 1 (SIRT1), a lysine deacetylase implicated in nutrient-dependent life span extension in mammals. Despite being cultured in normal (5.5 mM) glucose for 7 days, EOCs from diabetic rats expressed less SIRT1 mRNA, induced less endothelial tube formation in vitro and neovascularization in vivo, and secreted less of the proangiogenic ELR+ CXC chemokines CXCL1, CXCL3, and CXCLS. Ex vivo SIRT1 activation restored EOC chemokine secretion and increased the in vitro and in vivo angiogenic activity of EOC conditioned medium derived from diabetic animals to levels similar to that derived from control animals. These findings suggest a pivotal role for SIRT1 in diabetes-induced EOC dysfunction and that its pharmacologic activation may provide a new strategy for the restoration of EOC-mediated repair mechanisms. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:921-926

引用

页码：921 / 926

页数：6

共 17 条

[1] Novel Cell-Free Strategy for Therapeutic Angiogenesis: In Vitro Generated Conditioned Medium Can Replace Progenitor Cell Transplantation [J].