Resveratrol inhibits angiotensin II‑induced proliferation of A7r5 cells and decreases neointimal hyperplasia by inhibiting the CaMKII‑HDAC4 signaling pathway

Lin,Xiaozhen; Cheng,Chuanfang; Zhong,Junyang; Liu,Benrong; Luo,Chengfeng; Ou,Wenchao; Mo,Pei; Huang,Qiang; Liu,Shiming

doi:10.3892/mmr.2018.9056

Resveratrol inhibits angiotensin II‑induced proliferation of A7r5 cells and decreases neointimal hyperplasia by inhibiting the CaMKII‑HDAC4 signaling pathway

Authors:
- Xiaozhen Lin
- Chuanfang Cheng
- Junyang Zhong
- Benrong Liu
- Chengfeng Luo
- Wenchao Ou
- Pei Mo
- Qiang Huang
- Shiming Liu
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Affiliations: Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China
Published online on: May 23, 2018 https://doi.org/10.3892/mmr.2018.9056
Pages: 1007-1014

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Abstract

Resveratrol has been reported to inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia following arterial injury; however, the underlying mechanisms remain unclear. The present study was designed to investigate the effects of resveratrol on angiotensin II (AngII)‑induced proliferation of A7r5 cells and explore the molecular mechanisms responsible for the observed effects. Resveratrol inhibited cell proliferation and migration, and decreased the AngII‑induced protein expression of α‑smooth muscle actin (α‑SMA), proliferating cell nuclear antigen (PCNA) and cyclin‑dependent kinase 4 (CDK4). Resveratrol inhibited AngII‑induced activation of intracellular Ca2+/calmodulin‑dependent protein kinase II (CaMKII) and histone deacetylases 4 (HDAC4), as well as blocking AngII‑induced cell cycle progression from the G0/G1 to S‑phase. In vivo, 4‑weeks of resveratrol treatment decreased the neointima area and the neointima/media area ratio in rats following carotid balloon injury. Resveratrol also inhibited the protein expression of total and phosphorylated CaMKII and HDAC4 in the injured arteries. In conclusion, the present study demonstrated that resveratrol attenuated AngII‑induced cell proliferation and neointimal hyperplasia by inhibiting the CaMKII‑HDAC4 signaling pathway. These findings suggest that resveratrol may potentially prevent arterial restenosis.

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