Parathyroid hormone-related peptide as a local regulator of vascular calcification - Its inhibitory action on in vitro calcification by bovine vascular smooth muscle cells
Parathyroid hormone-related peptide as a local regulator of vascular calcification - Its inhibitory action on in vitro calcification by bovine vascular smooth muscle cells
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DOI：
10.1161/01.atv.17.6.1135
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发表时间：
1997-06-01
影响因子：
8.7
通讯作者：
Morii, H
中科院分区：
文献类型：
--
作者：
Jono, S;Nishizawa, Y;Morii, H
在本研究中，我们通过体外钙化模型研究了甲状旁腺激素相关肽（PTHrP）在血管钙化中的作用。我们证明了PTHrP的表达在牛血管平滑肌细胞（BVSMC）钙化的过程中下降，而依地酮酸（EHDP）和左旋咪唑抑制钙化可以恢复PTHrP的分泌，这表明PTHrP的表达与钙化有关。PTHrP（1-34）和PTH（1-34）呈剂量依赖性抑制BVSMC钙化。蛋白激酶A （PKA）和蛋白激酶C （PKC）抑制剂完全阻断了PTHrP的抑制作用，提示PKA和PKC可能参与了PTHrP的信号通路。此外，PTHrP抑制碱性磷酸酶（ALP）活性，表明对ALP的影响可能与其对钙化的作用有关。此外，PTHrP拮抗剂PTHrP（7-34）可以剂量依赖性地增加BVSMC的钙沉积。有趣的是，在EHDP的存在下，BVSMC产生的PTHrP显著增加，PTHrP（7-34）部分拮抗EHDP对BVSMC钙化的抑制作用。这些结果表明PTHrP可能作为一种自分泌/旁分泌因子调节血管钙化。
In the present study, we investigated the role of parathyroid hormone-related peptide (PTHrP) in vascular calcification by using an in vitro calcification model. We demonstrated that the expression of PTHrP decreased in the progression of bovine vascular smooth muscle cell (BVSMC) calcification and that inhibition of calcification by etidronate (EHDP) and levamisole restored PTHrP secretion, suggesting that the expression of PTHrP is associated with calcification. PTHrP (1-34) and PTH (1-34) dose-dependently inhibited BVSMC calcification. Protein kinase A (PKA) and protein kinase C (PKC) inhibitors completely blocked the inhibitory effect of PTHrP, suggesting that both PKA and PKC may be involved in its signaling pathway. Moreover, PTHrP inhibited alkaline phosphatase (ALP) activity, implying that the impact on ALP may contribute to its action on calcification. Furthermore, the PTHrP antagonist, PTHrP (7-34), dose-dependently increased calcium deposition by BVSMC. Interestingly, PTHrP production by BVSMC dramatically increased in the presence of EHDP, and PTHrP (7-34) partially antagonized the inhibitory effect of EHDP on BVSMC calcification. These results suggest that PTHrP may regulate vascular calcification as an autocrine/paracrine factor.