TY - JOUR
T1 - Effects of (-)-Epicatechin on Myocardial Infarct Size and Left Ventricular Remodeling After Permanent Coronary Occlusion
AU - Yamazaki, Katrina Go
AU - Taub, Pam R.
AU - Barraza-Hidalgo, Maraliz
AU - Rivas, Maria M.
AU - Zambon, Alexander C.
AU - Ceballos, Guillermo
AU - Villarreal, Francisco J.
N1 - Funding Information:
This study was supported by predoctoral award T32-HL007444 to Dr. Yamazaki and by National Institutes of Health grants HL-43617 and AT-004277 to Dr. Villarreal. Dr. Taub is supported by an American College of Cardiology/Merck Fellowship. Dr. Zambon is supported by an NIGMS IRACDA program . Dr. Ceballos is supported by a visiting professor CONACYT fellowship from Mexico. W. H. Wilson Tang, MD, served as Guest Editor for this paper.
PY - 2010/6/22
Y1 - 2010/6/22
N2 - Objectives: We examined the effects of the flavanol (-)-epicatechin on short- and long-term infarct size and left ventricular (LV) structure and function after permanent coronary occlusion (PCO) and the potential involvement of the protective protein kinase B (AKT)/extracellular signal-related kinase (ERK) signaling pathways. Background: (-)-epicatechin reduces blood pressure in hypertensive patients and limits infarct size in animal models of myocardial ischemia-reperfusion injury. However, nothing is known about its effects on infarction after PCO. Methods: (-)-epicatechin (1 mg/kg daily) treatment was administered via oral gavage to 250 g male rats for 10 days before PCO and was continued afterward. The PCO controls received water. Sham animals underwent thoracotomy and treatment in the absence of PCO. Immunoblots assessed AKT/ERK involvement 2 h after PCO. The LV morphometric features and function were measured 48 h and 3 weeks after PCO. Results: In the 48-h group, treatment reduced infarct size by 52%. There were no differences in hemodynamics among the different groups (heart rate and aortic and LV pressures). Western blots revealed no differences in AKT or ERK phosphorylation levels. At 3 weeks, PCO control animals demonstrated significant increases in LV end-diastolic pressure, heart and body weight, and LV chamber diameter versus sham. The PCO plus (-)-epicatechin group values were comparable with those of the sham plus (-)-epicatechin group. Treatment resulted in a 33% decrease in myocardial infarction size. The LV pressure-volume curves demonstrated a right shift in control PCO animals, whereas the (-)-epicatechin curves were comparable with those of the sham group. The LV scar area strains were significantly improved with (-)-epicatechin. Conclusions: These results demonstrate the unique capacity of (-)-epicatechin to confer cardioprotection in the setting of a severe form of myocardial ischemic injury. Protection is sustained over time and preserves LV structure and function. The cardioprotective mechanism(s) of (-)-epicatechin seem to be unrelated to AKT or ERK activation. (-)-epicatechin warrants further investigation as a cardioprotectant.
AB - Objectives: We examined the effects of the flavanol (-)-epicatechin on short- and long-term infarct size and left ventricular (LV) structure and function after permanent coronary occlusion (PCO) and the potential involvement of the protective protein kinase B (AKT)/extracellular signal-related kinase (ERK) signaling pathways. Background: (-)-epicatechin reduces blood pressure in hypertensive patients and limits infarct size in animal models of myocardial ischemia-reperfusion injury. However, nothing is known about its effects on infarction after PCO. Methods: (-)-epicatechin (1 mg/kg daily) treatment was administered via oral gavage to 250 g male rats for 10 days before PCO and was continued afterward. The PCO controls received water. Sham animals underwent thoracotomy and treatment in the absence of PCO. Immunoblots assessed AKT/ERK involvement 2 h after PCO. The LV morphometric features and function were measured 48 h and 3 weeks after PCO. Results: In the 48-h group, treatment reduced infarct size by 52%. There were no differences in hemodynamics among the different groups (heart rate and aortic and LV pressures). Western blots revealed no differences in AKT or ERK phosphorylation levels. At 3 weeks, PCO control animals demonstrated significant increases in LV end-diastolic pressure, heart and body weight, and LV chamber diameter versus sham. The PCO plus (-)-epicatechin group values were comparable with those of the sham plus (-)-epicatechin group. Treatment resulted in a 33% decrease in myocardial infarction size. The LV pressure-volume curves demonstrated a right shift in control PCO animals, whereas the (-)-epicatechin curves were comparable with those of the sham group. The LV scar area strains were significantly improved with (-)-epicatechin. Conclusions: These results demonstrate the unique capacity of (-)-epicatechin to confer cardioprotection in the setting of a severe form of myocardial ischemic injury. Protection is sustained over time and preserves LV structure and function. The cardioprotective mechanism(s) of (-)-epicatechin seem to be unrelated to AKT or ERK activation. (-)-epicatechin warrants further investigation as a cardioprotectant.
KW - cardioprotection
KW - catechins
KW - flavanols
KW - infarction
KW - ischemia
UR - http://www.scopus.com/inward/record.url?scp=77953308194&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2010.01.055
DO - 10.1016/j.jacc.2010.01.055
M3 - Artículo
C2 - 20579545
SN - 0735-1097
VL - 55
SP - 2869
EP - 2876
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 25
ER -