CPI-17-mediated contraction of vascular smooth muscle is essential for the development of hypertension in obese mice

作     者：Jie Sun Tao Tao Wei Zhao Lisha Wei Fan She Pei Wang Yeqiong Li Yanyan Zheng Xin Chen Wei Wang Yanning Qiao Xue-Na Zhang Min-Sheng Zhu 

作者机构：Model Animal Research Center and MOE Key Laboratory of Model Animal and Disease Study Nanjing University Key Laboratory of MOE for Modern Teaching Technology Shaanxi Normal University 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2019年第46卷第3期

页      面：109-118页

核心收录：

学科分类：10[医学] 

基　　金：supported by the National Natural Science Funding of China (31272311 and 31330034 to M.S.Z.) 

主　　题：CPI-17 Calcium sensitization Obesity-related hypertension 

摘      要：Several factors have been implicated in obesity-related hypertension, but the genesis of the hypertension is largely unknown. In this study, we found a significantly upregulated expression of CPI-17(C-kinasepotentiated protein phosphatase 1 inhibitor of 17 kDa) and protein kinase C(PKC) isoforms in the vascular smooth muscles of high-fat diet(HFD)-fed obese mice. The obese wild-type mice showed a significant elevation of blood pressure and enhanced calcium-sensitized contraction of vascular smooth muscles. However, the obese CPI-17-deficient mice showed a normotensive blood pressure, and the calcium-sensitized contraction was consistently reduced. In addition, the mutant muscle displayed an abolished responsive force to a PKC activator and a 30%-50% reduction in both the initial peak force and sustained force in response to various G protein-coupled receptor(GPCR) agonists. Our observations showed that CPI-17-mediated calcium sensitization is mediated through a GPCR/PKC/CPI-17/MLCP/RLC signaling pathway. We therefore propose that the upregulation of CPI-17-mediated calcium-sensitized vasocontraction by obesity contributes to the development of obesity-related hypertension.