title: Impact of remote physiological ischemic training on vascular endothelial growth factor, endothelial progenitor cells and coronary angiogenesis after myocardial ischemia.
abstract: OBJECTIVE
  This experimental study investigates the potential role of physiological ischemic training (PIT) of remote limbs on vascular endothelial growth factor (VEGF), endothelial progenitor cells (EPCs) and myocardial angiogenesis after myocardial ischemia.
  
  
  METHODS
  Forty-two rabbits were assigned into six groups at random: sham-operated (SO), training only (TO), myocardial ischemia (MI), PIT, EPC promoter (PIT+), and EPC inhibitor (PIT-). MI was experimentally induced by implanting a constrictor around the left ventricular branch. The PIT procedure included three 3-min cycles of cuff inflations on the hind limbs followed by a 5 min reperfusion. VEGF mRNA, protein and EPC numbers were measured in plasma and myocardium. Capillary density (CD), coronary blood flow (CBF) and coronary collateral blood flow (CCBF) were also determined.
  
  
  RESULTS
  Groups were compared using non-parametric statistics and associations between agents were explored with fractional polynomial regression. VEGF-mRNA and -protein levels were highest in PIT+ and PIT. PIT differed significantly from SO, TO, MI, and PIT- regarding VEGF-mRNA and -protein in plasma and VEGF-protein in myocardium. EPCs were highest in PIT+ followed by PIT. PIT differed significantly from SO, TO, MI, and PIT- regarding plasma EPCs. CD, CCBF and CCBF/CBF were significantly increased in PIT+ and PIT as compared to controls. PIT- did not differ significantly from SO and TO. VEGF explained up to 43% of variance in EPCs. EPCs explained up to 87% of variance in CD. CD explained up to 97% of variance in CCBF and CCBF/CBF.
  
  
  CONCLUSIONS
  PIT stimulates VEGF-mediated mobilization of EPCs as well as angiogenesis and might be proven as a new treatment strategy for patients with coronary heart disease.
authors.affiliation: The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Institute for Disaster Management and Reconstruction, Sichuan University-Hong Kong Polytechnic University, Chengdu, China; Interdisciplinary Division of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: luxiao1972@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: lijianan@carm.org.cn.
authors.forename: Jianan
authors.initials: J
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Qingsha
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute for Disaster Management and Reconstruction, Sichuan University-Hong Kong Polytechnic University, Chengdu, China; Swiss Paraplegic Research, Nottwil, Switzerland; University of Lucerne, Department of Health Sciences and Health Policy, Lucerne, Switzerland.
authors.forename: Jan D
authors.initials: JD
authors.lastname: Reinhardt
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood* / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000379:methods / Q000502:physiology*; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A
keywords: Capillary density; Coronary collateral circulation; Endothelial progenitor cells; Myocardial ischemia; Physiological ischemic training; Vascular endothelial growth factor