Impact of Resveratrol on Cardiac Remodeling in Female Rats: Emphasizing the Need for Sex-Specific Research

BACKGROUND: Menopause induces estrogen deficiency and promotes a pro-inflammatory and pro-fibrotic cardiovascular environment that increases susceptibility to adverse remodeling after myocardial infarction (MI). This study evaluated resveratrol as an inflammatory modulator and assessed its effects on cardiac fibrosis and hypertrophy in aged ovariectomized Wistar rats with chronic MI. METHODS: Thirty-six, one-year-old female Wistar rats (450-500 g) were allocated to six groups (n = 6 per group), with or without resveratrol treatment: (1) Sham, (2) Sham-R, (3) Bilateral ovariectomy (OVX), (4) OVX-R, (5) OVX + left anterior descending coronary artery ligation (LADL); OVX-LADL, and (6) OVX-LADL-R. Structural alterations, collagen deposition, and inflammatory profiles were assessed using histological analysis, morphometric measurements, and correlation-based heatmap. LADL in ovariectomized rats resulted in marked structural disorganization, increased cardiac fibrosis, and a predominance of pro-inflammatory mediators. RESULTS: Resveratrol treatment attenuated collagen deposition, partially preserved tissue architecture, and shifted the inflammatory profile towards a less pro-fibrotic pattern. Heatmap analysis showed that resveratrol reduced the strength of correlations between inflammatory markers and fibrotic remodeling, particularly in estrogen-deficient animals. CONCLUSION: These findings suggest that resveratrol attenuates adverse cardiac remodeling after MI in ovariectomized rats by modulating inflammation-driven fibrosis under estrogen-deficient conditions a response associated with increased IFN-γ.