Verapamil inhibits calcification and matrix vesicle activity of bovine vascular smooth muscle cells
Verapamil inhibits calcification and matrix vesicle activity of bovine vascular smooth muscle cells
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DOI：
10.1038/ki.2009.481
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发表时间：
2010-03-01
影响因子：
19.6
通讯作者：
Moe, Sharon M.
中科院分区：
文献类型：
--
作者：
Chen, Neal X.;Kircelli, Fatih;Moe, Sharon M.
血管平滑肌细胞中的钙通道活性是血管钙化和基质囊泡形成过程中的关键组成部分。在这里，我们研究了L-型钙通道的阻断是否会抑制这些功能。将牛血管平滑肌细胞或大鼠主动脉器官培养物在已知可促进钙化的培养基中孵育，并用L型钙通道抑制剂维拉帕米、硝苯地平或尼莫地平处理。苯烷基胺，维拉帕米，显着降低钙化的血管平滑肌细胞和大鼠主动脉，以剂量依赖性的方式，而二氢吡啶类，硝苯地平和尼莫地平，没有效果。此外，维拉帕米，而不是硝苯地平，显着降低牛血管平滑肌细胞的碱性磷酸酶活性。维拉帕米预处理的细胞也抑制基质囊泡碱性磷酸酶活性，并降低这些基质囊泡的能力，随后钙化的I型胶原细胞外基质支架。由于L-型通道被维拉帕米和二氢吡啶类药物阻断，我们认为维拉帕米抑制血管平滑肌矿化和基质囊泡活性的机制，而不是简单地阻断这种钙通道活性。Kidney International（2010）77，436-442; doi：10.1038/ki.2009.481; 2009年12月16日在线发表
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. Kidney International (2010) 77, 436-442; doi:10.1038/ki.2009.481; published online 16 December 2009