Atorvastatin Reduces Calcification in Rat Arteries and Vascular Smooth Muscle Cells

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 Ca2+ levels in the CA and AT groups were significantly higher than those before treatment and in the untreated controls. Plasma Ca2+ 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 mu M) for 24 hr. Cells in the calcification (CA) group and the AT group were cultured with beta-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 Ca2+ concentration. In vitro, AT reduced calcification markers in rat aortic vascular smooth muscle cells.