Resveratrol Attenuates Pressure Overload‐Induced Cardiac Fibrosis and Diastolic Dysfunction via PTEN/AKT/Smad2/3 and NF‐κB Signaling Pathways

Abstract

ScopeCardiac fibrosis is a key feature of cardiac remodeling. Recently, a protective role for resveratrol (RES) in pressure‐overload‐induced cardiac hypertrophy and contractile dysfunction has been demonstrated. However, the effect of RES on cardiac fibrosis and diastolic function in this model remains unclear.Methods and resultsCardiac remodeling is induced in mice by transverse aortic constriction (TAC) for 2–4 weeks. RES is administered at dose of 5 or 50 mg kg–1 d–1 for 2 weeks. It is found that RES administration at 50 mg kg–1 d–1 significantly attenuates TAC‐induced adverse cardiac systolic and diastolic function, fibrosis, inflammation, and oxidative stress via inhibiting PTEN degradation and the downstream mediators. However, RES at 5 mg kg–1 d–1 has no significant effects. RES at 50 mg kg–1 d–1 also ameliorates pre‐established adverse cardiac function and remodeling induced by TAC. Treatment with PTEN inhibitor VO‐OHpic (10 mg kg–1 d–1) for 2 weeks abolishes RES‐mediated protective effects. Additionally, the effect of RES (100 µm) on inhibition of Ang II‐induced fibroblast proliferation and activation in vitro is verified.ConclusionsThe findings provide new evidence that RES plays a critical role in the progression of cardiac fibrosis and diastolic dysfunction, and suggest that RES may be a promising therapeutic agent for cardiac fibrosis.

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction

“…In addition, the mRNA expression of inflammatory cytokines in diabetic mice are largely inhibited by resveratrol (Xing et al, 2020). Inflammation-related signaling pathways, such as NF-κB (Ma et al, 2020), Smad2/3 (Zou et al, 2019), and HSP70 (Khafaga et al, 2019), are also blocked by resveratrol. In the present study, we found that resveratrol modulated mitochondrial ROS production through affecting mitochondrial respiration complex I and III activities.…”

Gallic Acid Ameliorates Angiotensin II-Induced Atrial Fibrillation by Inhibiting Immunoproteasome- Mediated PTEN Degradation in Mice

“…Recent studies have demonstrated that phosphatase PTEN (a phosphatase and TENsin homolog deleted from chromosome 10) exhibits negative regulation of AT1R-induced signaling pathways and AF ( Li et al, 2018 , 2019 ). Importantly, we and others have revealed that the activity of PTEN is restored by natural compounds such as resveratrol and indole-3-carbinol ( Chen et al, 2019 ; Lee et al, 2019 ; Zou et al, 2019 ). Thus, regulation of PTEN represents a promising strategy for treating cardiovascular disease.…”

Resveratrol attenuates angiotensin II-induced cellular hypertrophy through the inhibition of CYP1B1 and the cardiotoxic mid-chain HETE metabolites

“…Several cardioprotective effects of resveratrol have been previously reported in various experimental and clinical settings. Experimentally, it attenuated pressure overloadinduced cardiac fibrosis and diastolic dysfunction, it protected against chronic intermittent hypoxia-induced cardiac hypertrophy and it also restored the cardiac function and structure in case of pressure overload-induced cardiac hypertrophy [24,25,48]. Clinically, multiple reports provided evidences that resveratrol exerts protective effects on the cardiovascular system in patients with coronary artery diseases in the secondary prevention against myocardial infarction.…”

“…In addition, it inhibited TCDD-mediated induction of CYP1B1 in cultured human mammary epithelial cells and human breast cancer cell line MCF-7 [22,23]. Several reports have demonstrated that resveratrol protects against cardiac hypertrophy through modulation of various pathways [24][25][26]. However, none of these studies investigated the effects of resveratrol on CYP1B1.…”