Effect of calcium channel blockers on the growth of human vascular smooth muscle cells derived from saphenous vein and vascular graft stenoses.
Vascular restenosis after invasive interventions is an important clinical problem for which no preventive pharmacologic therapy exists. Calcium channel blockers have been shown to inhibit myointimal hyperplasia in animal models of restenosis and in some small and flawed clinical coronary restenosis trials. We examined the inhibitory effect of amlodipine, verapamil, and diltiazem on the growth of cultured human vascular smooth muscle cells (VSMC) derived from saphenous vein (n = 20) and graft stenoses (n = 7), in 14-day proliferation assays and [methyl 3H]thymidine uptake studies. Amlodipine and verapamil produced significant inhibition (30%) of VSMC proliferation and DNA synthesis at 10 microM but not at 500 nM-1 microM. To our knowledge, this is the first study to examine the antiproliferative effect of calcium channel blockers in VSMC derived from human graft stenoses. Growth inhibition of VSMC from graft stenoses was not significantly different from that of control saphenous vein-derived cells. We conclude, therefore, that calcium channel blockers inhibit human VSMC proliferation in vitro, regardless of whether the cells were grown from graft stenoses or saphenous vein. However, the concentrations at which these calcium channel blockers elicit antiproliferative effects may not be attainable during therapeutic dosing in humans.
Munro
E
E
Department of Clinical Pharmacology, St. Mary's Hospital and Medical School, Imperial College of Science, Technology and Medicine, London, England.
Patel
M
M
Chan
P
P
Betteridge
L
L
Gallagher
K
K
Schachter
M
M
Wolfe
J
J
Sever
P
P
D017311:Amlodipine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004110:Diltiazem / Q000494:pharmacology*; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects / Q000637:transplantation; D014700:Verapamil / Q000494:pharmacology*
D017311:Amlodipine; D004247:DNA; D014700:Verapamil; D007770:L-Lactate Dehydrogenase; D004110:Diltiazem