SDF-1 promotes ox-LDL induced vascular smooth muscle cell proliferation

Cell Biol Int. 2013 Sep;37(9):988-94. doi: 10.1002/cbin.10126. Epub 2013 May 30.

Abstract

The mechanism of the regulatory roles of stromal cell derived factor-1 (SDF-1)/C-X-C motif receptor 4 (CXCR4) on cell proliferation and apoptosis in vascular smooth muscle cells (VSMCs) via the protein kinase C (PKC) and nuclear factor-kappa B (NF-κB) signalling pathways have been investigated. Rat aortic VSMCs were treated with control or an oxidised low-density lipoprotein (ox-LDL) atherosclerosis (AS) model. Cells exposed to the AS model were treated with SDF-1 plus inhibitors specific for PKC (Ro31-8220), CXCR4 (12G5) or NF-κB (pyrrolidine dithiocarbamate, PDTC). Cell proliferation was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis by flow cytometry. NF-κB protein expression was analysed using Western blotting. The proliferation rate in the AS model group was significantly higher than the control group, but lower than the SDF-1 group (P < 0.05). Apoptosis in the AS model group (ox-LDL) was significantly higher than the normal control group (P < 0.05). In addition, the apoptosis rate in the SDF-1 group was significantly lower than the normal control group (P < 0.05); however, there was no difference from the Ro31-8220 group. NF-κB protein expression in the SDF-1 group was significantly higher than the AS model (ox-LDL) group (P < 0.05). In conclusion, SDF-1 can promote the proliferation of VSMCs induced by ox-LDL and inhibit cell apoptosis, via the SDF-1/CXCR4 axis.

Keywords: NF-κB; SDF-1; ox-LDL; protein kinase C; smooth muscle cells.

MeSH terms

  • Animals
  • Aorta / cytology
  • Aorta / drug effects*
  • Aorta / metabolism
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Chemokine CXCL12 / genetics*
  • Chemokine CXCL12 / metabolism
  • Gene Expression Regulation / drug effects
  • Indoles / pharmacology
  • Lipoproteins, LDL / pharmacology*
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Signal Transduction
  • Thiocarbamates / pharmacology

Substances

  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Cxcr4 protein, rat
  • Indoles
  • Lipoproteins, LDL
  • NF-kappa B
  • Pyrrolidines
  • Receptors, CXCR4
  • Thiocarbamates
  • oxidized low density lipoprotein
  • pyrrolidine dithiocarbamic acid
  • Protein Kinase C
  • Ro 31-8220