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

Abstract

SCOPE:

Cardiac 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 RESULTS:

Cardiac 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.

CONCLUSIONS:

The 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.

• Authors: Lei-Xin Zou, Chen Chen, Xiao Yan, Qiu-Yue Lin, Jiao Fang, Pang-Bo Li, Xiao Han, Qing-Shan Wang, Shu-Bin Guo, Hui-Hua Li, Yun-Long Zhang
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 63 Issue 24 Pg. e1900418 (12 2019) ISSN: 1613-4133 [Electronic] Germany
• PMID: 31655498 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Cardiotonic Agents
• NF-kappa B
• Smad2 Protein
• Smad2 protein, mouse
• Smad3 Protein
• Smad3 protein, mouse
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• Pten protein, mouse
• Resveratrol

Topics

• Animals
• Cardiotonic Agents (pharmacology)
• Diastole (drug effects)
• Fibrosis
• Heart (drug effects, physiopathology)
• Male
• Mice, Inbred C57BL
• Myocarditis (drug therapy, etiology)
• Myocardium (pathology)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• PTEN Phosphohydrolase (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Resveratrol (pharmacology)
• Signal Transduction (drug effects)
• Smad2 Protein (metabolism)
• Smad3 Protein (metabolism)