Resveratrol attenuates pressure overload-induced myocardial remodeling in ovariectomized rats by rescuing the adaptive angiogenic response

BACKGROUND: Resveratrol (RES), a polyphenol with putative estrogen (E2) -like effects, is believed to counteract left ventricular hypertrophy (LVH). However, how RES exerts its protection is not well understood, particularly when prominent risk factors, such as E2 depletion and pressure overload (PO), coexist. Here, we evaluated the impact of RES and E2 on angiogenesis and LVH in rats subjected to ovariectomy (OVX) and PO. METHODS: Three weeks after bilateral OVX induction, abdominal aortic banding was performed on Wistar female rats to trigger PO. The animals were treated with either RES or E2 for six weeks. Finally, the heart-to-body weight ratio (HW/BW), cell size, fibrosis, and atrial natriuretic peptide (ANP) mRNA expression were assessed. Angiogenesis was determined by evaluating vascular endothelial growth factor (VEGF) mRNA and protein expression and by CD31 immunostaining. Serum E2 levels were also measured. RESULTS: OVX + PO caused more severe myocardial hypertrophy (HW/BW) and fibrosis compared with PO alone, but did not aggravate cell size and ANP mRNA expression. OVX blunted the angiogenic response to PO, with reduced VEGF expression. RES increased VEGF expression and CD31, and abrogated LVH and fibrosis. E2 treatment improved VEGF expression and fibrosis, but not to the same extent as RES. RES improved serum levels of E2 in OVX + PO rats. CONCLUSION: Our findings suggest that RES limits OVX-induced exacerbation of LVH and fibrosis in a PO model, and targets systemic E2 levels and myocardial angiogenesis as underpinning protective mechanisms. Thus, RES may provide cardioprotection for post-menopausal women.