Apocynin attenuates angiotensin II-induced vascular smooth muscle cells osteogenic switching via suppressing extracellular signal-regulated kinase 1/2

Weijing Feng, Kun Zhang, Yu Liu, Jie Chen, Qingqing Cai, Yinyin Zhang, Mong-Heng Wang, Jingfeng Wang, Hui Huang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Vascular calcification (VC) is a significant risk factor for cardiovascular morbidity and mortality. We recently reported that apocynin had benefits for preventing cardiovascular diseases. However, whether apocynin could attenuate VC is unknown. Here, we investigated the role of apocynin in VC and its underlying mechanisms. 163 participants with high or normal ankle-brachial index (ABI) were enrolled in this study for analyzing the demographic and biochemical data. In vitro, vascular smooth muscle cells (VSMCs) were exposed to calcification medium containing b-glycerophosphate and angiotensin II (Ang II) for 24 hours. The results showed that serum level of Ang II was significantly increased in patients with high ABI (P < 0.05). In cultured VSMCs, Ang II significantly exacerbated osteogenic switching. The expression of osteogenic phenotype markers, including bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2) and osteopontin (OPN), were significantly upregulated, whereas contractile markers expression, including alpha smooth muscle actin (a-SMA) and smooth muscle 22 alpha (SM22a) were simultaneously downregulated. However, these effects were greatly attenuated by apocynin. Apocynin enhanced expression of a-SMA by 5.3%, and reduced expression of BMP2, Runx2, OPN by 3.37%, 0.61% and 3.07%, respectively. Furthermore, extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was upregulated by Ang II, and this effect was also reversed by apocynin. Intriguingly, pretreatment with U0126, an inhibitor of ERK1/2, had similar effects with apocynin. Apocynin may act as a novel molecular candidate to protect against VSMCs osteogenic switching through suppressing ERK1/2 pathway.

Original languageEnglish (US)
Pages (from-to)83588-83600
Number of pages13
JournalOncotarget
Volume7
Issue number50
DOIs
StatePublished - 2016

Keywords

  • Angiotensin II
  • Apocynin
  • Osteogenic switching
  • Vascular calcification
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Oncology

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