TY - JOUR
T1 - Apocynin attenuates angiotensin II-induced vascular smooth muscle cells osteogenic switching via suppressing extracellular signal-regulated kinase 1/2
AU - Feng, Weijing
AU - Zhang, Kun
AU - Liu, Yu
AU - Chen, Jie
AU - Cai, Qingqing
AU - Zhang, Yinyin
AU - Wang, Mong-Heng
AU - Wang, Jingfeng
AU - Huang, Hui
N1 - Funding Information:
This work was supported in part by National Natural Science Foundation of China (NSFC) [81670676, 81422011 and 81370837], the Natural Science Foundation of Guangdong Province [2014A030313035], Guangzhou science and technology project [2060404] to Hui Huang and NSFC [81500563] to Jie Chen.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Angiotensin II
KW - Apocynin
KW - Osteogenic switching
KW - Vascular calcification
KW - Vascular smooth muscle cells
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U2 - 10.18632/oncotarget.13193
DO - 10.18632/oncotarget.13193
M3 - Article
C2 - 27835878
AN - SCOPUS:85003819955
SN - 1949-2553
VL - 7
SP - 83588
EP - 83600
JO - Oncotarget
JF - Oncotarget
IS - 50
ER -