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

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

doi:10.1016/j.jgg.2019.02.005

Volume 46 Issue 3

Mar. 2019

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Article Navigation > Journal of Genetics and Genomics > 2019 > 46(3): 109-118

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

doi: 10.1016/j.jgg.2019.02.005

a
Model Animal Research Center and MOE Key Laboratory of Model Animal and Disease Study, Nanjing University, Nanjing, 210061, China
b
Key Laboratory of MOE for Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China

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Corresponding author: E-mail address: zhangxn@nicemice.cn (Xue-Na Zhang); E-mail address: zhums@nju.edu.cn (Min-Sheng Zhu)
Received Date: 2018-12-03
Accepted Date: 2019-02-20
Rev Recd Date: 2019-01-21

Available Online: 2019-03-15

Publish Date: 2019-03-20

Abstract

Abstract

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-kinase-potentiated 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.
- CPI-17,
- Calcium sensitization,
- Obesity-related hypertension

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