title: Stimulatory effects of the flavanol (-)-epicatechin on cardiac angiogenesis:  additive effects with exercise.
abstract: The consumption of moderate amounts of cocoa products has been associated with reductions in the incidence of cardiovascular diseases. In animal studies, the flavanol (-)-epicatechin (Epi) yields cardioprotection. The effects may be partly due to its capacity to stimulate endothelial nitric oxide synthase (eNOS). The sustained activation of eNOS, as observed with exercise, can serve as a trigger of muscle angiogenesis via the activation of vascular endothelial growth factor (VEGF)-related events. Experiments were pursued to examine the potential of Epi to stimulate myocardial angiogenesis and determine the effects that its combined use with exercise (Ex) may trigger. Hearts obtained from a previous study were used for this purpose. Animals received 1 mg/kg of Epi or water (vehicle) via oral gavage (twice daily). Epi and/or Ex (by treadmill) was provided for 15 days. Results indicate that Ex or Epi significantly stimulate myocardial angiogenesis by ~30% above control levels. The use of Epi-Ex lead to further significant increases (to ~50%). Effects were associated with increases in protein levels and/or activation of canonical angiogenesis pathway associated events (HIF1a, VEGF, VEGFR2, PI3K, PDK, AKT, eNOS, NO, cGMP, MMP-2/-9, Src-1, and CD31). Thus, the use of Epi may represent a safe and novel means to stimulate myocardial angiogenesis.
authors: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Israel
authors: I
authors: Ramirez-Sanchez
authors: Leonardo
authors: L
authors: Nogueira
authors: Aldo
authors: A
authors: Moreno
authors: Ann
authors: A
authors: Murphy
authors: Pam
authors: P
authors: Taub
authors: Guy
authors: G
authors: Perkins
authors: Guillermo M
authors: GM
authors: Ceballos
authors: Michael
authors: M
authors: Hogan
authors: Moh
authors: M
authors: Malek
authors: Francisco
authors: F
authors: Villarreal
mesh_terms: D000284:Administration, Oral; D043925:Angiogenesis Inducing Agents / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000097:blood / Q000494:pharmacology*; D002392:Catechin / Q000097:blood / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D005080:Exercise Test; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: D043925:Angiogenesis Inducing Agents; D002316:Cardiotonic Agents; D009569:Nitric Oxide; D002392:Catechin; D006152:Cyclic GMP