title: Verapamil inhibits calcification and matrix vesicle activity of bovine vascular smooth muscle cells.
abstract: Calcium channel activity in vascular smooth muscle cells is a critical component during vascular calcification and formation of matrix vesicles. Here, we examined whether the blockade of L-type calcium channels inhibits these functions. Bovine vascular smooth muscle cells or rat aorta organ cultures were incubated in media known to promote calcification and treated with the L-type calcium channel inhibitors verapamil, nifedipine, or nimodipine. The phenylalkylamine, verapamil, significantly decreased calcification of the vascular smooth muscle cells and rat aorta, in a dose-dependent manner, whereas the dihydropyridines, nifedipine and nimodipine, had no effect. Furthermore, verapamil, but not nifedipine, significantly decreased the alkaline phosphatase activity of bovine vascular smooth muscle cells. Verapamil pretreatment of the cells also inhibited matrix vesicle alkaline phosphatase activity and reduced the ability of these matrix vesicles to subsequently calcify on a type I collagen extracellular matrix scaffold. As L-type channels are blocked by verapamil and dihydropyridines, we suggest that verapamil inhibits vascular smooth muscle mineralization and matrix vesicle activity by mechanisms other than the simple blockade of this calcium channel activity.
authors.affiliation: Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. xuechen@iupui.edu
authors.forename: Neal X
authors.initials: NX
authors.lastname: Chen
authors.forename: Fatih
authors.initials: F
authors.lastname: Kircelli
authors.forename: Kalisha D
authors.initials: KD
authors.lastname: O'Neill
authors.forename: Xianming
authors.initials: X
authors.lastname: Chen
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002113:Calcification, Physiologic / Q000187:drug effects*; D002114:Calcinosis / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D009924:Organ Culture Techniques; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D014700:Verapamil