Open AccessPeriod 2 is essential to maintain early endothelial progenitor cell function in vitro and angiogenesis after myocardial infarction in mice
Author(s) -
Sun YuanYuan,
Bai WenWu,
Wang Bo,
Lu XiaoTing,
Xing YiFan,
Cheng Wen,
Liu XiaoQiong,
Zhao YuXia
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12241
Subject(s) - angiogenesis , progenitor cell , neovascularization , endothelial progenitor cell , protein kinase b , therapeutic angiogenesis , pi3k/akt/mtor pathway , in vivo , medicine , biology , endocrinology , cancer research , immunology , microbiology and biotechnology , signal transduction , stem cell
Cellular therapeutic neovascularization has been successfully performed in clinical trials for patients with ischaemia diseases. Despite the vast knowledge of cardiovascular disease and circadian biology, the role of the circadian clock in regulating angiogenesis in myocardial infarction ( MI ) remains poorly understood. In this study, we aimed to investigate the role and underlying mechanisms of Period 2 (Per2) in endothelial progenitor cell ( EPC ) function. Flow cytometry revealed lower circulating EPC proportion in per2 −/− than in wild‐type ( WT ) mice. PER 2 was abundantly expressed in early EPC s in mice. In vitro , EPC s from per2 −/− mice showed impaired proliferation, migration, tube formation and adhesion. Western blot analysis demonstrated inhibited PI 3k/Akt/FoxO signalling and reduced C‐X‐C chemokine receptor type 4 ( CXCR 4) protein level in EPC s of per2 −/− mice. The impaired proliferation was blocked by activated PI 3K/Akt/FoxO signalling. Direct interaction of CXCR 4 and PER 2 was detected in WT EPC s. To further study the effect of per2 on in vivo EPC survival and angiogenesis, we injected saline or DiI‐labelled WT or per2 −/− EPC intramyocardially into mice with induced MI . Per2 −/− reduced the retention of transplanted EPC s in the myocardium, which was associated with significantly reduced DiI expression in the myocardium of MI mice. Decreased angiogenesis in the myocardium of per2 −/− EPC ‐treated mice coincided with decreased LV function and increased infarct size in the myocardium. Per2 may be a key factor in maintaining EPC function in vitro and in therapeutic angiogenesis in vivo .