Resveratrol significantly improved metabolic disturbance, reduced systolic BP, and ameliorated LV diastolic dysfunction (P<0.05) in diet-induced obese hypertensive rats.
RCT (n=24)
randomized
Does resveratrol improve myocardial fibrosis and LV diastolic dysfunction in a diet-induced obese hypertensive rat model?
Resveratrol improves metabolic profiles, reduces blood pressure, and attenuates myocardial fibrosis and LV diastolic dysfunction via the TGF-β/Smad pathway in a rat model of obesity and hypertension.
p-value: p=<0.05
Objective: Obesity-induced myocardial fibrosis contributes to left ventricular (LV) diastolic dysfunction and eventually heart failure. Resveratrol is a polyphenol that has been reported to have anti-diabetic, anti-fibrotic, and cardio-protective effects. We investigated whether resveratrol could ameliorate myocardial fibrosis and LV diastolic dysfunction in high-fat diet (HFD)-induced obese hypertensive model.Design and method: Eight-week-old male Wistar-Kyoto rats (WKY, n=8) and spontaneously hypertensive rats (SHR) fed an HFD were randomized to receive resveratrol (25 mg/kg/day; SHR-HFD-R, n=8) or vehicle (control; SHR-HFD-C, n=8) for 12 weeks. At 20 weeks, the metabolic profiles, blood pressure (BP), and echocardiographic parameters were assessed. Myocardial fibrosis was evaluated histologically, and myocardial expression of transforming growth factor-β1 (TGF-β1), collagen I, and phosphorylated Smad2/3 was quantified. In vitro, rat cardiac fibroblasts were stimulated with TGF-β1 to evaluate the effects of resveratrol on fibrosis-related signaling. Results: Compared with WKY, SHR-HFD-C developed marked hypertension, hyperglycemia, dyslipidemia, and perivascular fibrosis. Resveratrol significantly improved metabolic disturbance, reduced systolic BP, and ameliorated LV diastolic dysfunction (E/A ratio, 1.38±0.05 vs. 1.57±0.11; E/e’, 26.8±7.7 vs. 17.9±3.6; both P<0.05). However, LV hypertrophy and systolic dysfunction remained unchanged. Furthermore, resveratrol markedly reduced myocardial fibrosis and collagen production, and downregulated myocardial TGF-β1 expression and Smad2/3 phosphorylation. In vitro, resveratrol suppressed TGF-β1–induced collagen production and Smad2/3 activation in cardiac fibroblasts. Conclusions: Diet-induced obese hypertensive rats exhibited elevated BP, metabolic disturbance, LV diastolic dysfunction, and aggravated myocardial fibrosis. Resveratrol effectively improved metabolic and hemodynamic profiles and reduced fibrosis through modulation of the TGF-β/Smad pathway, suggesting translational potential for obesity-related hypertensive heart disease.
Ihm et al. (2026) conducted an RCT in Obesity-induced myocardial fibrosis and hypertension (n=24). Resveratrol vs. Vehicle was evaluated on LV diastolic dysfunction (E/A ratio and E/e') (p=<0.05). Resveratrol significantly improved metabolic disturbance, reduced systolic BP, and ameliorated LV diastolic dysfunction (P<0.05) in diet-induced obese hypertensive rats.