HMGB1 Silencing Potentiates the Anti-inflammatory Effects of Sodium Ferulate in ox-LDL-Stimulated Vascular Smooth Muscle Cells

作者:Hu, Nan; Kong, Lingshang; Qian, Aimin; Meng, Qingyou; Li, Chenglong; Yu, Xiaobin; Chen, Hong; Du, Xiaolong; Li, Xiaoqiang*
来源:Cell Biochemistry and Biophysics, 2015, 72(1): 297-304.
DOI:10.1007/s12013-014-0455-x

摘要

Atherosclerosis is a sustained inflammatory disease of the arterial wall. The purpose of the current study is to investigate the effect of sodium ferulate on the proliferation and migration of human vascular smooth muscle cells (hVSMCs). In addition, we also sought to determine whether HMGB1 knockdown could potentiate the anti-inflammatory effects of sodium ferulate. hVSMCs were treated with oxidized lower-density lipoprotein (ox-LDL, 50 mg/l) to induce inflammation. Cells were then treated with sodium ferulate and HMGB1 silencing (SiHMGB1) individually or in combination. The phenotypes of the treated cells including proliferation, cell cycle profile, apoptosis, and gene expression were analyzed. Results showed that sodium ferulate or SiHMGB1 treatment inhibited ox-LDL-induced inflammation in hVSMCs. Furthermore, the combination of SiHMGB1 plus sodium ferulate treatment displayed an additive effect in inhibiting the proliferation and migration of hVSMCs. Consistently, the suppression of receptor for advanced glycation end products expression was also observed. ICAM-1 and transforming growth factor-beta suggest that these signaling components were involved in the anti-inflammatory effect. Our study confirms the anti-inflammatory function of sodium ferulate, and uncovered the potentiating effect of HMGB1 knockdown in suppressing ox-LDL-induced proliferation and migration of hVSMCs. Inhibition of HMGB1 expression in addition to sodium ferulate treatment might be a more effective therapeutic approach for atherosclerosis.

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