The role of losartan in preventing vascular remodeling in spontaneously hypertensive rats by inhibition of the H2O2/VPO1/HOCl/MMPs pathway
The role of losartan in preventing vascular remodeling in spontaneously hypertensive rats by inhibition of the H2O2/VPO1/HOCl/MMPs pathway
复制标题
氯沙坦通过抑制 H2O2/VPO1/HOCl/MMPs 通路预防自发性高血压大鼠血管重塑的作用
DOI：
10.1016/j.bbrc.2017.06.026
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发表时间：
2017-11-04
影响因子：
3.1
通讯作者：
Shi, Ruizheng
中科院分区：
文献类型：
--
作者：
Ge, Liangqing;Zhang, Guogang;Shi, Ruizheng
血管过氧化物酶1（VPO 1）通过产生活性氧参与血管内皮细胞凋亡。然而，VPO 1对血管重塑（VR）发展的贡献仍有待充分表征。本研究旨在探讨VPO 1在自发性高血压大鼠（SHR）VR中的作用及氯沙坦抑制VR的可能机制。与Wistar-Kyoto（WKY）大鼠相比，SHR表现出血管壁重塑。VPO 1水平和过氧化氢（H2 O2）浓度在SHR中增加。然而，与未处理的SHR相比，氯沙坦预处理的SHR显示出显著的血压和VR抑制以及VPO 1和H2 O2水平降低。血管紧张素II可显著增加血管平滑肌细胞（VSMCs）中MMP-2、MMP-9的表达及H_2O_2、HOCl浓度。而VPO 1 shRNA转染后，VSMCs中H2 O2水平升高。这些结果支持VPO 1在VR中的关键但以前未被认识的作用，并表明减少VPO 1的疗法可能是VR的新方法。(C)2017爱思唯尔公司All rights reserved.
Vascular peroxidase 1 (VPO1) has been proved to be associated with vascular endothelial cell apoptosis by producing reactive oxygen species. However, the contribution of VPO1 to the development of vascular remodeling (VR) remains to be fully characterized. We explored the role of VPO1 in VR in spontaneously hypertensive rats (SHRs) and the underlying mechanism of losartan in inhibiting VR. Compared to Wistar-Kyoto (WKY) rats, the SHR showed remodeling of their vascular walls. The level of VPO1 and the hydrogen peroxide (H2O2) concentration were increased in the SHRs. However, the SHRs pretreated with losartan showed significant inhibition of blood pressure and VR and decreased levels of VPO1 and H2O2 compared to the non-treated SHRs. Angiotensin II significantly increased the expressions of MMP-2, MMP-9 and the concentrations of H2O2 and hypochlorous acid (HOCl) in vascular smooth muscle cells (VSMCs). However, only the H2O2 level increased in VSMCs when transfected with VPO1 shRNA. These results support a critical but previously unrecognized role of VPO1 in VR and suggest that therapies to reduce VPO1 may be novel approaches for VR. (C) 2017 Elsevier Inc. All rights reserved.