Open AccessHigh glucose impairs the proliferation and increases the apoptosis of endothelial progenitor cells by suppression of Akt
Author(s) -
Nakamura Nobuhisa,
Naruse Keiko,
Kobayashi Yasuko,
Matsuki Takashi,
Hamada Yoji,
Nakashima Eitaro,
Kamiya Hideki,
Hata Masaki,
Nishikawa Toru,
Enomoto Atsushi,
Takahashi Masahide,
Murohara Toyoaki,
Matsubara Tatsuaki,
Oiso Yutaka,
Nakamura Jiro
Publication year - 2011
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/j.2040-1124.2010.00093.x
Subject(s) - progenitor cell , protein kinase b , endothelial progenitor cell , medicine , vasculogenesis , vascular endothelial growth factor , endocrinology , phosphorylation , apoptosis , cd34 , cancer research , stem cell , microbiology and biotechnology , biology , vegf receptors , biochemistry
Aims/Introduction: Endothelial progenitor cells (EPC) play a critical role in adult vasculogenesis and vascular repair. Previous studies have described the dysfunction of EPC in diabetic patients, but the precise mechanism is still unclear. To elucidate the dysfunction of EPC in diabetic patients, we investigated the functions and intracellular signaling of EPC under normal or high glucose conditions. We also examined the number of EPC in the peripheral blood of Japanese type 2 diabetic patients. Materials and Methods: EPC were cultured with normal or high glucose. Subsequently, the proliferation and the apoptosis of EPC were assessed in the presence or absence of vascular endothelial growth factor (VEGF). The phosphorylation of Akt was assessed by western blot analyses. We compared the number of CD34 + CD45 low progenitor cells, which is considered as a marker of EPC in non‐diabetic and type 2 diabetic subjects, using flow cytometry. Results: High glucose decreased the proliferation of EPC and increased the number of apoptotic cells. VEGF significantly increased the proliferation and suppressed the apoptosis of EPC, both of which were abolished by PI 3‐kinase inhibitor, LY294002. High glucose significantly suppressed the basal and VEGF‐stimulated phosphorylation of Akt in EPC. Furthermore, the number of circulating EPC was decreased in type 2 diabetic patients, although there were no significant differences in the serum levels of VEGF between control subjects and diabetic patients. Conclusions: These findings suggest that high glucose impairs the functions of EPC through the suppression of Akt phosphorylation stimulated by VEGF. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00093.x, 2011)