Impact of remote physiological ischemic training on vascular endothelial growth factor, endothelial progenitor cells and coronary angiogenesis after myocardial ischemia

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. Conclusion: 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.