title: Period2 deficiency blunts hypoxia-induced mobilization and function of endothelial progenitor cells.
abstract: BACKGROUND
  In the clinic, variations in circadian rhythm are evident in patients with cardiovascular disease, and the risk of cardiovascular events increases when rhythms are disrupted. In this study, we focused on the role of the circadian gene period2 (per2) in mobilization and function of endothelial progenitor cells (EPCs) in vitro and in vivo after myocardial infarction (MI) in mice.
  
  
  RESULTS
  MI was produced by surgical ligation of the left anterior descending coronary artery in mice with and without per2 deficiency. Trans-thoracic echocardiography was used to evaluate cardiac function in mice. Per2-/- mice with MI showed decreased cardiac function and increased infarct size. The number of CD34+ cells and capillary density were decreased in the myocardium of per2-/- mice on immunohistochemistry. Flow cytometry revealed decreased number of circulating EPCs in per2-/- mice after MI. In vitro, per2-/- EPCs showed decreased migration and tube formation capacity under hypoxia. Western blot analysis revealed inhibited activation of extracellular signal-regulated kinase and Akt signaling in the bone marrow of per2-/- mice and inhibited PI3K/Akt expression in per2-/- EPCs under hypoxia.
  
  
  CONCLUSIONS
  Per2 modulates EPC mobilization and function after MI, which is important to recovery after MI in mice.
authors.affiliation: Department of Emergency Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Jinan, Shandong, China; Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Sun
authors.affiliation: Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Wen-Wu
authors.initials: WW
authors.lastname: Bai
authors.affiliation: Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Xing
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Jinan, Shandong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Jinan, Shandong, China.
authors.forename: Rui-Xue
authors.initials: RX
authors.lastname: Yang
authors.affiliation: Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Li
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D015687:Cell Hypoxia; D002465:Cell Movement; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases