Involvement of mitochondrial fission in calcium sensing receptor-mediated vascular smooth muscle cells proliferation during hypertension

Biochem Biophys Res Commun. 2018 Jan 1;495(1):454-460. doi: 10.1016/j.bbrc.2017.11.048. Epub 2017 Nov 8.

Abstract

Hyperproliferation of vascular smooth muscle cells (VSMC) is a major risk factor for cardiovascular diseases. Proper mitochondrial fission and fusion is involved with VSMC function. However, the role and mechanism of mitochondrial morphological changes in VSMC proliferation are not well understood. Here, we found that calcium sensing receptor (CaSR) was increased in the aortas from spontaneous hypertensive rats (SHRs) compared with age-matched Wistar Kyoto (WKY) rats. There was also an increase in mitochondrial fission and VSMC proliferation, which was attenuated by Calhex231. In primary rat VMSC, angiotensin II (Ang II) stimulation induced cytosolic [Ca2+]i increase, mitochondrial shortening and proliferation, all of which could be attenuated by pretreatment with mitochondrial division inhibitor-1 (Mdivi-1) and Calhex231. Our data indicate that CaSR-mediated mitochondrial fission could be a therapeutic target for hyperproliferative disorders.

Keywords: Calcium sensing receptor; Hypertension; Mitochondrial fission; Proliferation; Vascular smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Aorta / physiopathology*
  • Benzamides / pharmacology
  • Benzamides / therapeutic use
  • Blood Pressure / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclohexylamines / pharmacology
  • Cyclohexylamines / therapeutic use
  • Hypertension / drug therapy
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • Male
  • Mitochondrial Dynamics* / drug effects
  • Molecular Targeted Therapy
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiopathology*
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Rats, Wistar
  • Receptors, Calcium-Sensing / analysis
  • Receptors, Calcium-Sensing / antagonists & inhibitors
  • Receptors, Calcium-Sensing / metabolism*

Substances

  • Benzamides
  • Cyclohexylamines
  • N(1)-(4-chlorobenzoyl)-N(2)-(1-(1-naphthyl)ethyl)-1,2-diaminocyclohexane
  • Receptors, Calcium-Sensing