Vericiguat attenuates cardiac inflammation and oxidative stress in an obese postmenopausal rat model with concurrent modulation of PKG-I, TGF-β1, and NF-κB

Inflammation and oxidative stress are implicated in cardiometabolic changes associated with menopause and obesity. This study investigated the effects of Vericiguat (VER) alone and in combination with estradiol (E2) on oxidative, inflammatory, atherogenic and fibrosis-related markers in cardiac tissue in an ovariectomized rat model of diet-induced obesity. Female Wistar rats were divided into sham and ovariectomized (OVX) groups and fed a standard diet (SD) or high-fat diet (HFD) for 4 months, followed by 4 weeks of treatment with E2, two doses of VER, or their combination. Body weight, malondialdehyde (MDA), total antioxidant capacity (TAC), plasma atherogenic index (AIP), cardiac risk indices I and II (CRI-I and CRI-II), cardiac hydroxyproline, and expression of cardiac PKG-I, NF-κB, and TGF-β1 proteins were assessed. OVX and HFD were associated with increased body weight, AIP, CRI-I, CRI-II, MDA, cardiac NF-κB and TGF-β1 expression, and hydroxyproline content, along with decreased TAC, TAC/MDA ratio, and PKG-I expression. E2 and VER treatments improved these alterations, as evidenced by reductions in AIP, CRI-I, CRI-II, MDA, NF-κB, TGF-β1, and hydroxyproline, as well as increases in TAC, TAC/MDA ratio, and PKG-I expression. Combined treatment with E2 and VER, compared to treatment with E2 alone, significantly improved all these parameters, with the exception of CRI-I and CRI-II. There were significant interactions between E2 and VER treatments were observed for TAC/MDA, hydroxyproline content, and TGF-β1 expression. VER and E2 ameliorated several oxidative, inflammatory, atherogenic, and fibrosis-related changes in this model.