Suppression of lysophosphatidylcholine-induced human aortic smooth muscle cell calcification by protein kinase A inhibition
Suppression of lysophosphatidylcholine-induced human aortic smooth muscle cell calcification by protein kinase A inhibition
复制标题
抑制蛋白激酶 A 抑制溶血磷脂酰胆碱诱导的人主动脉平滑肌细胞钙化
DOI：
10.1002/lipd.12178
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发表时间：
2019
期刊：
影响因子：
1.9
通讯作者：
Jeong-Hun Kang
中科院分区：
文献类型：
--
作者：
Riki Toita;Daisuke Asai;Kentaro Otani;Takahito Kawano;Masaharu Murata;Jeong-Hun Kang
溶血磷脂酰胆碱（lysoPtdCho）主要由磷脂酶A2依赖性水解磷脂酰胆碱（PtdCho）产生，可诱导血管平滑肌细胞中的炎症激活和成骨基因表达。然而，介导这些过程的机制尚未完全阐明。在这项研究中，我们研究了抑制蛋白激酶A（PKA）信号传导是否抑制了lysoPtdCho诱导的人主动脉平滑肌细胞（HASMC）钙化。与磷酸盐缓冲盐水处理的HASMC相比，用lysoPtdCho处理的HASMC中的钙水平和碱性磷酸酶活性显著增加，但PtdCho未增加。然而，PKA抑制剂（H-89）或PKA siRNA的加入阻断了lysoPtdCho诱导的HASMC钙化。这些结果表明，lysoPtdCho可以激活PKA介导的HASMC钙化，PKA可能是lysoPtdCho介导的血管平滑肌细胞钙化的治疗靶点。
Lysophosphatidylcholine (lysoPtdCho) is produced mainly by the phospholipase A2‐dependent hydrolysis of phosphatidylcholine (PtdCho) and can induce inflammatory activation and osteogenic gene expression in vascular smooth muscle cells. However, the mechanisms mediating these processes have not been fully elucidated. In this study, we investigated whether inhibition of protein kinase A (PKA) signaling suppressed lysoPtdCho‐induced calcification of human aortic smooth muscle cells (HASMC). Calcium levels and alkaline phosphatase activity were significantly increased in HASMC treated with lysoPtdCho, but not PtdCho, compared with those in phosphate‐buffered saline‐treated HASMC. However, the addition of a PKA inhibitor (H‐89) or PKA siRNA blocked lysoPtdCho‐induced HASMC calcification. These results showed that lysoPtdCho could activate PKA‐mediated HASMC calcification and that PKA may be a therapeutic target for lysoPtdCho‐mediated vascular smooth muscle cell calcification.