Benidipine, a dihydropyridine-calcium channel blocker, prevents lysophosphatidylcholine-induced injury and reactive oxygen species production in human aortic endothelial cells
Benidipine, a dihydropyridine-calcium channel blocker, prevents lysophosphatidylcholine-induced injury and reactive oxygen species production in human aortic endothelial cells
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DOI：
10.1016/j.atherosclerosis.2004.08.020
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发表时间：
2005-01-01
期刊：
影响因子：
5.3
通讯作者：
Hasegawa, K
中科院分区：
文献类型：
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作者：
Matsubara, M;Hasegawa, K
溶血磷脂酰胆碱 (lysoPC) 是氧化低密度脂蛋白 (oxLDL) 的组成部分。在动脉粥样硬化的发病机制中起重要作用。在本研究中，我们检测了盐酸贝尼地平（贝尼地平）（一种具有抗氧化活性的二氢吡啶钙通道阻滞剂）是否可以预防 lysoPC (C 16:0) 诱导的人主动脉内皮细胞 (HAEC) 损伤。用 lysoPC 处理 HAEC 会改变细胞形态、降低细胞活力并诱导 DNA 断裂。导致细胞凋亡。此外，lysoPC 种类还含有棕榈酰基 (C 16:0) 或硬脂酰基 (C 18:0)。它们是oxLDL的主要成分。刺激活性氧 (ROS) 产生并诱导 HAEC 中的 caspase-3/7 样活性，但具有短酰基链的 lysoPC 物种不会影响 ROS 产生或 caspase-3/7 样活性。用贝尼地平 (0.3-3 mumol/L) 预处理 24 小时，可以防止内皮细胞中 lysoPC 诱导的细胞毒性，并且该药物以相似的效力抑制 lysoPC 刺激的 ROS 产生和 caspase-3/7 样激活。由于caspase-3/7参与细胞凋亡过程的执行，因此苯地平降低该酶的活性可能是该药物的抗细胞凋亡作用。然而，贝尼地平不能抑制 lysoPC 诱导的有丝分裂原激活蛋白激酶的磷酸化和 HAEC 中的 Ca2+ 流入。这些结果表明，贝尼地平的抗氧化特性可能是其抑制 ROS 产生的能力的原因，从而导致 caspase-3/7 的激活减少。总之，贝尼地平通过抑制 ROS 产生来抑制 lysoPC 诱导的内皮功能障碍。这至少部分归因于其抗氧化作用。并且不是通过抑制L型电压依赖性钙通道。 (C) 2004 Elsevier Ireland Ltd. 保留所有权利。
Lysophosphatidylcholine (lysoPC) is a component of oxidized low-density lipoproteins (oxLDLs). which play an important role in the pathogenesis of atherosclerosis. In this study, we examined whether benidipine hydrochloride (benidipine), a dihydropyridine-calcium channel blocker with antioxidant activity, prevents lysoPC (C 16:0)-induced injury of human aortic endothelial cells (HAEC). Treatment of HAECs with lysoPC changed cell morphology, decreased cell viability and induced DNA fragmentation. leading to apoptosis. Additionally lysoPC species containing palmitoyl (C 16:0) or stearoyl (C 18:0). which are the major components of oxLDLs. stimulated reactive oxygen species (ROS) production and induced caspase-3/7-like activity in HAECs, but lysoPC species with short acyl chains did not affect either ROS production or caspase-3/7-like activity. Pretreatment with benidipine (0.3-3 mumol/L) for 24 h protected against lysoPC-induced cytoxicity in the endothelial cells and the drug inhibited both lysoPC-stimulated ROS production and caspase-3/7-like activation with a similar potency. Since caspase-3/7 is involved in executing the apoptotic process, the reduction of the activity of this enzyme by benedipine may the anti-apoptotic effect of the drug. However, benidipine did not suppress lysoPC-induced phosphorylation of mitogen-activated protein kinases and Ca2+ influx in HAECs. These results suggest that the anti-oxidant properties of benidipine may be responsible for its ability to inhibit ROS production, resulting in reduced activation of caspase-3/7. In conclusion, benidipine suppresses lysoPC-induced endothelial dysfunction through inhibition of ROS production. which is due at least in part to its antioxidant effect. and not through the inhibition of L-type voltage-dependent calcium channels. (C) 2004 Elsevier Ireland Ltd. All rights reserved.