Modulation of calcification of vascular smooth muscle cells in culture by calcium antagonists, statins, and their combination.
BACKGROUND
Vascular calcification is an organized process in which vascular smooth muscle cells (VSMCs) are implicated primarily. The purpose of the present study was to assess the effects of calcium antagonists and statins on VSMC calcification in vitro.


METHODS
VSMC calcification was stimulated by incubation in growth medium supplemented with 10 mmol/l beta-glycerophosphate, 8 mmol/l CaCl(2), 10 mmol/l sodium pyruvate, 1 micromol/l insulin, 50 microg/ml ascorbic acid, and 100 nmol/l dexamethasone (calcification medium). Calcification, proliferation, and apoptosis of VSMCs were quantified.


RESULTS
Calcium deposition was stimulated dose-dependently by beta-glycerophosphate, CaCl(2), and ascorbic acid (all P < 0.01). Addition of amlodipine (0.01-1 micromol/l) to the calcification medium did not affect VSMC calcification. However, atorvastatin (2-50 micromol/l) stimulated calcium deposition dose-dependently. Combining treatments stimulated calcification to a degree similar to that observed with atorvastatin alone. Both atorvastatin and amlodipine inhibited VSMC proliferation at the highest concentration used. Only atorvastatin (50 micromol/l) induced considerable apoptosis of VSMCs.


CONCLUSIONS
In vitro calcification of VSMCs is not affected by amlodipine, but is stimulated by atorvastatin at concentrations > or =10 micromol/l, which could contribute to the plaque-stabilizing effect reported for statins.
Trion
Astrid
A
Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Schutte-Bart
Cindy
C
Bax
Wilhelmina H
WH
Jukema
J Wouter
JW
van der Laarse
Arnoud
A
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology; D000069059:Atorvastatin; D002114:Calcinosis / Q000473:pathology*; D002118:Calcium / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology*; D010710:Phosphates / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D006538:Heptanoic Acids; D010710:Phosphates; D011758:Pyrroles; D017311:Amlodipine; D003907:Dexamethasone; D000069059:Atorvastatin; D001205:Ascorbic Acid; D002118:Calcium