Acrolein-induced apoptosis of smooth muscle cells through NEAT1-Bmal1/Clock pathway and a protection from asparagus extract
2020
Chen, Lijun | Wu, Xiaoyue | Zeb, Falak | Huang, Yunxiang | An, Jing | Jiang, Pan | Chen, Aochang | Xu, Chuyue | Feng, Qing
Apoptosis of vascular smooth muscle cells (VSMCs) accelerates manifestation of plaque vulnerability in atherosclerosis. Long noncoding RNA NEAT1 participates in the proliferation and apoptosis of cells. In addition, circadian clock genes play a significant role in cell apoptosis. However, whether acrolein, an environmental pollutant, affects the apoptosis of VSMCs by regulating NEAT1 and clock genes is still elusive. We established VSMCs as an atherosclerotic cell model in vitro. Acrolein exposure reduced survival rate of VSMCs, and raised apoptosis percentage through upregulating the expression of Bax, Cytochrome c and Cleaved caspase-3 and downregulating Bcl-2. Asparagus extract (AE), as a dietary supplementation, was able to protect VSMCs against acrolein-induced apoptosis. Expression of NEAT1, Bmal1 and Clock was decreased by acrolein, while was ameliorated by AE. Knockdown of NEAT1, Bmal1 or Clock promoted VSMCs apoptosis by regulating Bax, Bcl-2, Cytochrome c and Caspase-3 levels. Correspondingly, overexpression of NEAT1 inhibited the apoptosis. We also observed that silence of NEAT1 repressed the expression of Bmal1/Clock and vice versa. In this study, we demonstrated that VSMCs apoptosis induced by acrolein was associated with downregulation of NEAT1 and Bmal1/Clock. AE alleviated the effects of proapoptotic response and circadian disorders caused by acrolein, which shed a new light on cardiovascular protection.
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