Atorvastatin reduces calcification in rat arteries and vascular smooth muscle cells

Basic Clin Pharmacol Toxicol. 2010 Oct;107(4):798-802. doi: 10.1111/j.1742-7843.2010.00580.x.

Abstract

To examine the in vivo effects of atorvastatin (AT) on arterial calcification in rats, arterial calcification was established by subcutaneous injection of vitamin D3 and Warfarin. Intragastric administration of AT began 4 days before establishment of arterial calcification in the AT group (n=6). Blood samples were taken and abdominal aortas were collected and stained. After induction of calcification, plasma Ca(2+) levels in the CA and AT groups were significantly higher than those before treatment and in the untreated controls. Plasma Ca(2+) levels in the AT group were significantly lower than in the CA group. The relative calcification area in aortic specimens from the AT group was significantly smaller than in the CA group. Rat aortic vascular smooth muscle cells (VMSC) were isolated from abdominal aortic segments and pre-treated with AT (1, 5, or 10 μM) for 24 hr. Cells in the calcification (CA) group and the AT group were cultured with β-glycerophosphate, insulin and vitamin C for 14 days to induce cell calcification. Calcium deposition and alkaline phosphatase activity were significantly increased in the CA group compared to untreated controls (p<0.01). This effect was ameliorated by AT (all p<0.01). In vivo administration of AT reduced arterial calcification and plasma Ca(2+) concentration. In vitro, AT reduced calcification markers in rat aortic vascular smooth muscle cells.

MeSH terms

  • Animals
  • Aorta, Abdominal / drug effects
  • Aorta, Abdominal / pathology
  • Atorvastatin
  • Calcinosis / chemically induced
  • Calcinosis / pathology
  • Calcinosis / prevention & control*
  • Calcium / blood
  • Cells, Cultured
  • Drug Combinations
  • Heptanoic Acids / pharmacology*
  • Heptanoic Acids / therapeutic use
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • In Vitro Techniques
  • Injections, Subcutaneous
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / pathology
  • Pyrroles / pharmacology*
  • Pyrroles / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Thoracic Arteries / drug effects
  • Thoracic Arteries / pathology
  • Vitamin D
  • Warfarin

Substances

  • Drug Combinations
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Vitamin D
  • Warfarin
  • Atorvastatin
  • Calcium