Effects of (-)-epicatechin on myocardial infarct size and left ventricular remodeling after permanent coronary occlusion
Katrina Go Yamazaki, Pam R Taub, Maraliz Barraza-Hidalgo, Maria M Rivas, Alexander C Zambon, Guillermo Ceballos, Francisco J Villarreal, Katrina Go Yamazaki, Pam R Taub, Maraliz Barraza-Hidalgo, Maria M Rivas, Alexander C Zambon, Guillermo Ceballos, Francisco J Villarreal
Abstract
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.
Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Figures
![Figure 1. Infarct area (IA) as a…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2915587/bin/nihms219032f1.jpg)
Figure 2. Infarct area (IA) as a…
Figure 2. Infarct area (IA) as a function of LV area 3 wks post-permanent coronary…
Figure 3. Average passive left ventricular pressure…
Figure 3. Average passive left ventricular pressure volume relations for sham (n=6; closed circles), sham…
Figure 4. Average two-dimensional circumferential (E 11…
Figure 4. Average two-dimensional circumferential (E 11 ) (A) and longitudinal (E 22 ) (B)…
Figure 5. ERK and AKT levels (AU=arbitrary…
Figure 5. ERK and AKT levels (AU=arbitrary units) in animals subjected to 10 days vehicle…
- Short- and long-term effects of (-)-epicatechin on myocardial ischemia-reperfusion injury.Yamazaki KG, Romero-Perez D, Barraza-Hidalgo M, Cruz M, Rivas M, Cortez-Gomez B, Ceballos G, Villarreal F. Yamazaki KG, et al. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H761-7. doi: 10.1152/ajpheart.00413.2008. Epub 2008 Jun 20. Am J Physiol Heart Circ Physiol. 2008. PMID: 18567705 Free PMC article.
- Early short-term treatment with doxycycline modulates postinfarction left ventricular remodeling.Villarreal FJ, Griffin M, Omens J, Dillmann W, Nguyen J, Covell J. Villarreal FJ, et al. Circulation. 2003 Sep 23;108(12):1487-92. doi: 10.1161/01.CIR.0000089090.05757.34. Epub 2003 Sep 2. Circulation. 2003. PMID: 12952845
- Effect of endurance training early or late after coronary artery occlusion on left ventricular remodeling, hemodynamics, and survival in rats with chronic transmural myocardial infarction.Gaudron P, Hu K, Schamberger R, Budin M, Walter B, Ertl G. Gaudron P, et al. Circulation. 1994 Jan;89(1):402-12. doi: 10.1161/01.cir.89.1.402. Circulation. 1994. PMID: 8281676
- Sphingosine-1-Phosphate Receptor Agonist Fingolimod Increases Myocardial Salvage and Decreases Adverse Postinfarction Left Ventricular Remodeling in a Porcine Model of Ischemia/Reperfusion.Santos-Gallego CG, Vahl TP, Goliasch G, Picatoste B, Arias T, Ishikawa K, Njerve IU, Sanz J, Narula J, Sengupta PP, Hajjar RJ, Fuster V, Badimon JJ. Santos-Gallego CG, et al. Circulation. 2016 Mar 8;133(10):954-66. doi: 10.1161/CIRCULATIONAHA.115.012427. Epub 2016 Jan 29. Circulation. 2016. PMID: 26826180
- Very mild hypothermia during ischemia and reperfusion improves postinfarction ventricular remodeling.Hamamoto H, Sakamoto H, Leshnower BG, Parish LM, Kanemoto S, Hinmon R, Plappert T, Miyamoto S, St John-Sutton MG, Gorman JH 3rd, Gorman RC. Hamamoto H, et al. Ann Thorac Surg. 2009 Jan;87(1):172-7. doi: 10.1016/j.athoracsur.2008.08.015. Ann Thorac Surg. 2009. PMID: 19101292 Free PMC article.
- Small ubiquitin-related modifier (SUMO)ylation of SIRT1 mediates (-)-epicatechin inhibited- differentiation of cardiac fibroblasts into myofibroblasts.Luo Y, Lu J, Wang Z, Wang L, Wu G, Guo Y, Dong Z. Luo Y, et al. Pharm Biol. 2022 Dec;60(1):1762-1770. doi: 10.1080/13880209.2022.2101672. Pharm Biol. 2022. PMID: 36086802 Free PMC article.
- (-)-Epicatechin Ameliorates Cardiac Fibrosis in a Female Rat Model of Pre-Heart Failure with Preserved Ejection Fraction.Bustamante-Pozo M, Ramirez-Sanchez I, Garate-Carrillo A, Ito B, Navarrete V, Haro M, Garcia R, Carson N, Ceballos G, Villarreal F. Bustamante-Pozo M, et al. J Med Food. 2022 Aug;25(8):836-844. doi: 10.1089/jmf.2021.0158. Epub 2022 Aug 2. J Med Food. 2022. PMID: 35917528
- Cardioprotective Effect of Rheum turkestanicum Against Doxorubicin-Induced Toxicity in Rats.Hosseini A, Safari MK, Rajabian A, Boroumand-Noughabi S, Eid AH, Al Dhaheri Y, Gumpricht E, Sahebkar A. Hosseini A, et al. Front Pharmacol. 2022 Jun 8;13:909079. doi: 10.3389/fphar.2022.909079. eCollection 2022. Front Pharmacol. 2022. PMID: 35754479 Free PMC article.
- Pharmacology of Catechins in Ischemia-Reperfusion Injury of the Heart.Ferenczyová K, Kindernay L, Vlkovičová J, Kaločayová B, Rajtík T, Barteková M. Ferenczyová K, et al. Antioxidants (Basel). 2021 Aug 30;10(9):1390. doi: 10.3390/antiox10091390. Antioxidants (Basel). 2021. PMID: 34573022 Free PMC article. Review.
- Mechanisms Modified by (-)-Epicatechin and Taxifolin Relevant for the Treatment of Hypertension and Viral Infection: Knowledge from Preclinical Studies.Bernatova I, Liskova S. Bernatova I, et al. Antioxidants (Basel). 2021 Mar 16;10(3):467. doi: 10.3390/antiox10030467. Antioxidants (Basel). 2021. PMID: 33809620 Free PMC article. Review.
- Comparative Study
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Administration, Oral
- Analysis of Variance
- Animals
- Catechin / pharmacology*
- Coronary Circulation
- Coronary Occlusion / diagnostic imaging
- Coronary Occlusion / drug therapy*
- Coronary Occlusion / mortality
- Disease Models, Animal
- Hemodynamics / physiology*
- Male
- Myocardial Infarction / drug therapy*
- Myocardial Infarction / mortality
- Myocardial Infarction / pathology
- Myocardial Infarction / prevention & control*
- Myocardial Reperfusion Injury / prevention & control
- Probability
- Radiography
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Reference Values
- Survival Rate
- Treatment Outcome
- Ventricular Remodeling / drug effects*
- Ventricular Remodeling / physiology
- Catechin
- Full Text Sources
- Medical
- Miscellaneous
NCBI Literature Resources
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![Figure 2. Infarct area (IA) as a…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2915587/bin/nihms219032f2.jpg)
Figure 3. Average passive left ventricular pressure…
Figure 3. Average passive left ventricular pressure volume relations for sham (n=6; closed circles), sham…
Figure 4. Average two-dimensional circumferential (E 11…
Figure 4. Average two-dimensional circumferential (E 11 ) (A) and longitudinal (E 22 ) (B)…
Figure 5. ERK and AKT levels (AU=arbitrary…
Figure 5. ERK and AKT levels (AU=arbitrary units) in animals subjected to 10 days vehicle…
- Short- and long-term effects of (-)-epicatechin on myocardial ischemia-reperfusion injury.Yamazaki KG, Romero-Perez D, Barraza-Hidalgo M, Cruz M, Rivas M, Cortez-Gomez B, Ceballos G, Villarreal F. Yamazaki KG, et al. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H761-7. doi: 10.1152/ajpheart.00413.2008. Epub 2008 Jun 20. Am J Physiol Heart Circ Physiol. 2008. PMID: 18567705 Free PMC article.
- Early short-term treatment with doxycycline modulates postinfarction left ventricular remodeling.Villarreal FJ, Griffin M, Omens J, Dillmann W, Nguyen J, Covell J. Villarreal FJ, et al. Circulation. 2003 Sep 23;108(12):1487-92. doi: 10.1161/01.CIR.0000089090.05757.34. Epub 2003 Sep 2. Circulation. 2003. PMID: 12952845
- Effect of endurance training early or late after coronary artery occlusion on left ventricular remodeling, hemodynamics, and survival in rats with chronic transmural myocardial infarction.Gaudron P, Hu K, Schamberger R, Budin M, Walter B, Ertl G. Gaudron P, et al. Circulation. 1994 Jan;89(1):402-12. doi: 10.1161/01.cir.89.1.402. Circulation. 1994. PMID: 8281676
- Sphingosine-1-Phosphate Receptor Agonist Fingolimod Increases Myocardial Salvage and Decreases Adverse Postinfarction Left Ventricular Remodeling in a Porcine Model of Ischemia/Reperfusion.Santos-Gallego CG, Vahl TP, Goliasch G, Picatoste B, Arias T, Ishikawa K, Njerve IU, Sanz J, Narula J, Sengupta PP, Hajjar RJ, Fuster V, Badimon JJ. Santos-Gallego CG, et al. Circulation. 2016 Mar 8;133(10):954-66. doi: 10.1161/CIRCULATIONAHA.115.012427. Epub 2016 Jan 29. Circulation. 2016. PMID: 26826180
- Very mild hypothermia during ischemia and reperfusion improves postinfarction ventricular remodeling.Hamamoto H, Sakamoto H, Leshnower BG, Parish LM, Kanemoto S, Hinmon R, Plappert T, Miyamoto S, St John-Sutton MG, Gorman JH 3rd, Gorman RC. Hamamoto H, et al. Ann Thorac Surg. 2009 Jan;87(1):172-7. doi: 10.1016/j.athoracsur.2008.08.015. Ann Thorac Surg. 2009. PMID: 19101292 Free PMC article.
- Small ubiquitin-related modifier (SUMO)ylation of SIRT1 mediates (-)-epicatechin inhibited- differentiation of cardiac fibroblasts into myofibroblasts.Luo Y, Lu J, Wang Z, Wang L, Wu G, Guo Y, Dong Z. Luo Y, et al. Pharm Biol. 2022 Dec;60(1):1762-1770. doi: 10.1080/13880209.2022.2101672. Pharm Biol. 2022. PMID: 36086802 Free PMC article.
- (-)-Epicatechin Ameliorates Cardiac Fibrosis in a Female Rat Model of Pre-Heart Failure with Preserved Ejection Fraction.Bustamante-Pozo M, Ramirez-Sanchez I, Garate-Carrillo A, Ito B, Navarrete V, Haro M, Garcia R, Carson N, Ceballos G, Villarreal F. Bustamante-Pozo M, et al. J Med Food. 2022 Aug;25(8):836-844. doi: 10.1089/jmf.2021.0158. Epub 2022 Aug 2. J Med Food. 2022. PMID: 35917528
- Cardioprotective Effect of Rheum turkestanicum Against Doxorubicin-Induced Toxicity in Rats.Hosseini A, Safari MK, Rajabian A, Boroumand-Noughabi S, Eid AH, Al Dhaheri Y, Gumpricht E, Sahebkar A. Hosseini A, et al. Front Pharmacol. 2022 Jun 8;13:909079. doi: 10.3389/fphar.2022.909079. eCollection 2022. Front Pharmacol. 2022. PMID: 35754479 Free PMC article.
- Pharmacology of Catechins in Ischemia-Reperfusion Injury of the Heart.Ferenczyová K, Kindernay L, Vlkovičová J, Kaločayová B, Rajtík T, Barteková M. Ferenczyová K, et al. Antioxidants (Basel). 2021 Aug 30;10(9):1390. doi: 10.3390/antiox10091390. Antioxidants (Basel). 2021. PMID: 34573022 Free PMC article. Review.
- Mechanisms Modified by (-)-Epicatechin and Taxifolin Relevant for the Treatment of Hypertension and Viral Infection: Knowledge from Preclinical Studies.Bernatova I, Liskova S. Bernatova I, et al. Antioxidants (Basel). 2021 Mar 16;10(3):467. doi: 10.3390/antiox10030467. Antioxidants (Basel). 2021. PMID: 33809620 Free PMC article. Review.
- Comparative Study
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Administration, Oral
- Analysis of Variance
- Animals
- Catechin / pharmacology*
- Coronary Circulation
- Coronary Occlusion / diagnostic imaging
- Coronary Occlusion / drug therapy*
- Coronary Occlusion / mortality
- Disease Models, Animal
- Hemodynamics / physiology*
- Male
- Myocardial Infarction / drug therapy*
- Myocardial Infarction / mortality
- Myocardial Infarction / pathology
- Myocardial Infarction / prevention & control*
- Myocardial Reperfusion Injury / prevention & control
- Probability
- Radiography
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Reference Values
- Survival Rate
- Treatment Outcome
- Ventricular Remodeling / drug effects*
- Ventricular Remodeling / physiology
- Catechin
- Full Text Sources
- Medical
- Miscellaneous
![Figure 3. Average passive left ventricular pressure…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2915587/bin/nihms219032f3.jpg)
Figure 4. Average two-dimensional circumferential (E 11…
Figure 4. Average two-dimensional circumferential (E 11 ) (A) and longitudinal (E 22 ) (B)…
Figure 5. ERK and AKT levels (AU=arbitrary…
Figure 5. ERK and AKT levels (AU=arbitrary units) in animals subjected to 10 days vehicle…
![Figure 4. Average two-dimensional circumferential (E 11…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2915587/bin/nihms219032f4.jpg)
![Figure 5. ERK and AKT levels (AU=arbitrary…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2915587/bin/nihms219032f5.jpg)
Source: PubMed