title: Neuropilin-1 is essential for enhanced VEGF(165)-mediated vasodilatation in collateral-dependent coronary arterioles of exercise-trained pigs.
abstract: OBJECTIVE
  Exercise training enhances vasodilatation to vascular endothelial growth factor (VEGF(165)) in collateral-dependent coronary arterioles. Interaction of VEGF receptor 2 (VEGFR-2) and the non-tyrosine-kinase receptor, neuropilin-1 has been reported to potentiate VEGF(165)-mediated signaling. In the current study, we tested the hypotheses that neuropilin-1 mediates the exercise-enhanced VEGF(165)-mediated vasodilatation in collateral-dependent arterioles and that neuropilin-1 and/or VEGFR-2 protein levels are increased in these arterioles.
  
  
  METHODS
  Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of miniature swine. Eight weeks after surgery, the animals were randomized into sedentary or exercise training (treadmill run; 5 days/week; 14 weeks) protocols. Coronary arterioles (approximately 100 microm diameter) were isolated from both collateral-dependent and control (left anterior descending) myocardial regions and studied by in vitro videomicroscopy or frozen for immunoblot analysis.
  
  
  RESULTS
  Exercise-enhanced VEGF(165)-mediated vasodilatation in collateral-dependent arterioles was reversed by inhibition of the VEGF(165)-neuropilin-1 interaction. VEGF(121), which does not interact with neuropilin-1, induced similar vasodilatation in arterioles from all treatment groups. Immunoblot revealed significantly elevated VEGFR-1, VEGFR-2 and neuropilin-1 protein levels in collateral-dependent arterioles of exercise-trained pigs.
  
  
  CONCLUSIONS
  Neuropilin-1 plays a vital role in the exercise-enhanced VEGF(165)-mediated vasodilatation of collateral-dependent coronary arterioles and is associated with increased neuropilin-1 receptor protein levels.
authors.affiliation: Department of Systems Biology and Translational Medicine, The Texas A&M University System Health Science Center, College Station, Tex., USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Fogarty
authors.forename: Michael D
authors.initials: MD
authors.lastname: Delp
authors.forename: Judy M
authors.initials: JM
authors.lastname: Muller-Delp
authors.forename: Glen A
authors.initials: GA
authors.lastname: Laine
authors.forename: Janet L
authors.initials: JL
authors.lastname: Parker
authors.forename: Cristine L
authors.initials: CL
authors.lastname: Heaps