Salusin-β induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFκB pathway.
Salusin-β induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFκB pathway.
复制标题
Salusin-beta 通过 miR155/NOX2/NFkappaB 途径诱导人血管平滑肌细胞泡沫细胞形成和单核细胞粘附。
DOI：
10.1038/srep23596
复制
发表时间：
2016-03-23
影响因子：
4.6
通讯作者：
Zhu GQ
中科院分区：
文献类型：
--
作者：
Sun HJ;Zhao MX;Liu TY;Ren XS;Chen Q;Li YH;Kang YM;Zhu GQ
血管平滑肌细胞（VSMC）是泡沫细胞形成的重要组成部分。Salusin-β是动脉粥样硬化进展中的刺激物。在此，我们发现salusin-β增加了人VSMC中的泡沫细胞形成（通过脂滴和细胞内胆固醇含量的积累证明），并促进了单核细胞粘附。Salusin-β可增加VSMC中酰基辅酶A：胆固醇酰基转移酶-1（ACAT-1）和血管细胞粘附分子-1（VCAM-1）的表达和活性。沉默ACAT-1可抑制salusin-β诱导的VSMCs脂质蓄积，沉默VCAM-1可抑制salusin-β诱导的VSMCs单核细胞粘附。Salusin-β可引起p65-NFκB核转位，并增加p65在ACAT-1和VCAM-1启动子区的占有率。Bay 11-7082抑制NFκB可抑制salusin-β诱导的VSMCs中ACAT-1和VCAM-1的上调、泡沫细胞形成和单核细胞粘附。清除ROS、抑制NADPH氧化酶或敲低NOX 2均能阻断salusin-β对VSMCs ACAT-1和VCAM-1表达、p65-NFκB核转位、脂质积聚和单核细胞粘附的影响。Salusin-β可上调miR 155的表达，而miR 155的敲低可抑制salusin-β对VSMCs ACAT-1和VCAM-1表达、p65-NFκB核转位、脂质积聚、单核细胞粘附和ROS产生的影响。这些结果表明salusin-β通过miR 155/NOX 2/NFκ B介导的ACAT-1和VCAM-1表达诱导VSMCs泡沫形成和单核细胞粘附。
Vascular smooth muscle cells (VSMCs) are indispensible components in foam cell formation. Salusin-β is a stimulator in the progression of atherosclerosis. Here, we showed that salusin-β increased foam cell formation evidenced by accumulation of lipid droplets and intracellular cholesterol content, and promoted monocyte adhesion in human VSMCs. Salusin-β increased the expressions and activity of acyl coenzyme A:cholesterol acyltransferase-1 (ACAT-1) and vascular cell adhesion molecule-1 (VCAM-1) in VSMCs. Silencing of ACAT-1 abolished the salusin-β-induced lipid accumulation, and silencing of VCAM-1 prevented the salusin-β-induced monocyte adhesion in VSMCs. Salusin-β caused p65-NFκB nuclear translocation and increased p65 occupancy at the ACAT-1 and VCAM-1 promoter. Inhibition of NFκB with Bay 11-7082 prevented the salusin-β-induced ACAT-1 and VCAM-1 upregulation, foam cell formation and monocyte adhesion in VSMCs. Scavenging ROS, inhibiting NADPH oxidase or knockdown of NOX2 abolished the effects of salusin-β on ACAT-1 and VCAM-1 expressions, p65-NFκB nuclear translocation, lipid accumulation and monocyte adhesion in VSMCs. Salusin-β increased miR155 expression, and knockdown of miR155 prevented the effects of salusin-β on ACAT-1 and VCAM-1 expressions, p65-NFκB nuclear translocation, lipid accumulation, monocyte adhesion and ROS production in VSMCs. These results indicate that salusin-β induces foam formation and monocyte adhesion via miR155/NOX2/NFκB-mediated ACAT-1 and VCAM-1 expressions in VSMCs.