TY - JOUR
T1 - Stimulatory effects of the flavanol (-)-epicatechin on cardiac angiogenesis
T2 - Additive effects with exercise
AU - Ramirez-Sanchez, Israel
AU - Nogueira, Leonardo
AU - Moreno, Aldo
AU - Murphy, Ann
AU - Taub, Pam
AU - Perkins, Guy
AU - Ceballos, Guillermo M.
AU - Hogan, Michael
AU - Malek, Moh
AU - Villarreal, Francisco
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
KW - angiogenesis
KW - flavonoids
KW - ischemia
KW - myocardium
UR - http://www.scopus.com/inward/record.url?scp=84870063237&partnerID=8YFLogxK
U2 - 10.1097/FJC.0b013e318269ae0d
DO - 10.1097/FJC.0b013e318269ae0d
M3 - Artículo
C2 - 22833114
SN - 0160-2446
VL - 60
SP - 429
EP - 438
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 5
ER -