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

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)

摘要

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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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doi: 10.1016/j.jgg.2019.02.005

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

Corresponding author: E-mail address: zhangxn@nicemice.cn (Xue-Na Zhang); E-mail address: zhums@nju.edu.cn (Min-Sheng Zhu)

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doi: 10.1016/j.jgg.2019.02.005

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

Corresponding author: E-mail address: zhangxn@nicemice.cn (Xue-Na Zhang); E-mail address: zhums@nju.edu.cn (Min-Sheng Zhu)

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