Effects of serotonin on expression of the LDL receptor family member LR11 and 7-ketocholesterol-induced apoptosis in human vascular smooth muscle cells
Effects of serotonin on expression of the LDL receptor family member LR11 and 7-ketocholesterol-induced apoptosis in human vascular smooth muscle cells
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DOI：
10.1016/j.bbrc.2014.03.031
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发表时间：
2014-04-18
影响因子：
3.1
通讯作者：
Taisuno, Ichiro
中科院分区：
文献类型：
--
作者：
Nagayama, Daiji;Ishihara, Noriko;Taisuno, Ichiro
5-羟色胺（5-HT）是已知的血管平滑肌细胞（VSMCs）的有丝分裂原。动脉内膜VSMCs的去分化和增殖/凋亡是动脉粥样硬化的重要病理改变之一。LR 11是低密度脂蛋白受体家族成员，可能参与了新生内膜增生中VSMCs的增殖。我们进行了一项体外研究，以调查是否5-HT参与LR 11在人VSMCs的表达和7-酮胆固醇（7 KCHO），不稳定斑块的氧化固醇诱导的VSMCs的凋亡。5-HT可促进VSMCs增殖，此作用可被5-HT 2A受体拮抗剂沙格雷酯阻断。沙格雷酯还抑制5-HT增强的VSMCs中LR 11 mRNA的表达。5-HT通过caspase-3/7依赖性途径抑制7 KCHO诱导的VSMCS凋亡。这些发现为5-HT介导的VSMCs分化阶段的变化提供了新的见解。(C)2014 Elsevier Inc. All rights reserved.
Serotonin (5-HT) is a known mitogen for vascular smooth muscle cells (VSMCs). The dedifferentiation and proliferation/apoptosis of VSMCs in the arterial intima represent one of the atherosclerotic changes. LR11, a member of low-density lipoprotein receptor family, may contribute to the proliferation of VSMCs in neointimal hyperplasia. We conducted an in vitro study to investigate whether 5-HT is involved in LR11 expression in human VSMCs and apoptosis of VSMCs induced by 7-ketocholesterol (7KCHO), anoxysterol that destabilizes plaque. 5-HT enhanced the proliferation of VSMCs, and this effect was abolished by sarpogrelate, a selective 5-HT2A receptor antagonist. Sarpogrelate also inhibited the 5-HT-enhanced LR11 mRNA expression in VSMCs. Furthermore, 5-HT suppressed the 7KCHO-induced apoptosis of VSMCS via caspase-3/7-dependent pathway. These findings provide new insights on the changes in the differentiation stage of VSMCs mediated by 5-HT. (C) 2014 Elsevier Inc. All rights reserved.