Related Experiment Video
Updated: Jul 18, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic
Suresh Varma Penumathsa1, Mahesh Thirunavukkarasu, Srikanth Koneru
1Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1110, USA.
Insights
Combination therapy with statin and resveratrol offers superior cardioprotection in a rat model of hypercholesterolemia and myocardial infarction. This approach enhances left ventricular function, reduces infarct size, and promotes beneficial vascularization.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Biochemistry
Background:
- Hypercholesterolemia (HC) significantly elevates cardiovascular disease risk.
- Statin (S) and resveratrol (R) provide cardioprotection via nitric oxide pathways.
- Investigating combination therapy for enhanced cardioprotective effects is warranted.
Purpose of the Study:
- To evaluate the cardioprotective efficacy of combined statin and resveratrol therapy compared to individual treatments in an ischemic rat heart model.
- To assess the impact of combination therapy on cardiac function, infarct size, lipid levels, apoptosis, and angiogenesis.
Main Methods:
- Rats with diet-induced hypercholesterolemia were treated with statin, resveratrol, or both.
- Hearts were subjected to global ischemia and reperfusion to model myocardial infarction.
- Left ventricular function, infarct size, lipid profiles, cardiomyocyte apoptosis, capillary density, and molecular markers (Akt, eNOS, VEGF) were analyzed.
Main Results:
- Combination therapy (HCRS) significantly improved left ventricular functional recovery and reduced infarct size compared to HC, HCS, and HCR groups.
- HCRS and HCS treatments led to greater lipid reduction than HCR.
- Increased Akt and eNOS phosphorylation, reduced cardiomyocyte apoptosis, enhanced capillary density, and elevated VEGF mRNA expression were observed, most notably in the HCRS group.
Conclusions:
- Combined statin and resveratrol therapy demonstrates superior cardioprotection against ischemia-reperfusion injury in hypercholesterolemic rats.
- The benefits are attributed to anti-hyperlipidemic, anti-apoptotic, pro-angiogenic effects, and enhanced neo-vascularization, leading to reduced ventricular remodeling.
Abstract:
Hypercholesterolemia (HC) is a common health problem that significantly increases risk of cardiovascular disease. Both statin (S) and resveratrol (R) demonstrated cardioprotection through nitric oxide-dependent mechanism. Therefore, the present study was undertaken to determine whether combination therapy with statin and resveratrol is more cardioprotective than individual treatment groups in ischemic rat heart model. The rats were fed with 2% high cholesterol diet and after 8 weeks of high cholesterol diet the animals were treated with statin (1 mg/kg bw/day) and resveratrol (20 mg/kg bw/day) for 2 weeks. The rats were assigned to: (1) Control (C), (2) HC, (3) HCR, (4) HCS and (5) HCRS. The hearts, subjected to 30-min global ischemia followed by 120-min reperfusion were used as experimental model. The left ventricular functional recovery (+dp/dt(max)) was found to be significantly better in the HCRS (1926+/-43), HCR (1556+/-65) and HCS (1635+/-40) compared to HC group (1127+/-16). The infarct sizes in the HCRS, HCS and HCR groups were 37+/-3.6, 43+/-3.3 and 44+/-4.2 respectively compared to 53+/-4.6 in HC. The lipid level was found to be decreased in all the treatment groups when compared to HC more significantly in HCS and HCRS groups when compared to HCR. Increased phosphorylation of Akt and eNOS was also observed in all the treatment groups resulting in decreased extent of cardiomyocyte apoptosis but the extent of reduction in apoptosis was more significant in HCRS group compared to all other groups. In vivo rat myocardial infarction (MI) model subjected to 1 week of permanent left descending coronary artery (LAD) occlusion documented increased capillary density in HCR and HCRS treated group when compared to HCS treatment group. We also documented increased beta-catenin translocation and increased VEGF mRNA expression in all treatment groups. Thus, we conclude that the acute as well as chronic protection afforded by combination treatment with statin and resveratrol may be due to pro-angiogenic, anti-hyperlipidemic and anti-apoptotic effects and long-term effects may be caused by increased neo-vascularization of the MI zone leading to less ventricular remodeling.
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