| First Author | Sun J | Year | 2019 |
| Journal | J Genet Genomics | Volume | 46 |
| Issue | 3 | Pages | 109-118 |
| PubMed ID | 30948334 | Mgi Jnum | J:290992 |
| Mgi Id | MGI:6443503 | Doi | 10.1016/j.jgg.2019.02.005 |
| Citation | Sun J, et al. (2019) CPI-17-mediated contraction of vascular smooth muscle is essential for the development of hypertension in obese mice. J Genet Genomics 46(3):109-118 |
| abstractText | 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 17kDa) 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. |
