Low-density lipoproteins induce the renin-angiotensin system and their receptors in human endothelial cells
Low-density lipoproteins induce the renin-angiotensin system and their receptors in human endothelial cells
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DOI：
10.1055/s-2007-991158
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发表时间：
2007-11-01
影响因子：
2.2
通讯作者：
Morawietz, H.
中科院分区：
文献类型：
--
作者：
Catar, R. A.;Mueller, G.;Morawietz, H.
低密度脂蛋白水平升高是内皮功能障碍和代谢综合征的公认危险因素。在这项研究中，我们评估了天然低密度脂蛋白（nLDL）和氧化低密度脂蛋白（oxLDL）对血管紧张素系统基因表达的影响（血管紧张素转换酶，ACE;血管紧张素11 I型受体，AT）及其受体（低密度脂蛋白受体：LDLR;凝集素样oxLDL受体：LOX-1; toll样受体4：TLR 4）在人脐静脉内皮细胞原代培养物中的表达。nLDL和oxLDL刺激后，ACE和AT表达均显著增加。OxLDL受体LOX-1在7小时后显示最大诱导。LOX-1特异性抗体可阻断LOX-1蛋白表达的增加。nLDL和oxLDL也能增加TLR 4的表达。我们的结论是，LDL和oxLDL可以激活人内皮细胞中的肾素-血管紧张素系统及其受体LDLR，LOX-1和TLR 4。这些数据表明代谢综合征患者的高胆固醇血症和高血压之间存在新的联系。
Increased levels of low-density lipoproteins are well-established risk factors of endothelial dysfunction and the metabolic syndrome. In this study, we evaluated the effect of native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL) on the expression of genes of the renin-angiotensin system (angiotensin-converting enzyme, ACE; angiotensin 11 type I receptor, AT,) and their receptors (low-density lipoprotein receptor: LDLR; lectin-like oxLDL receptor: LOX-1; toll-like receptor 4: TLR4) in primary cultures of human umbilical vein endothelial cells. ACE and AT, expressions were significantly increased after stimulation with nLDL and oxLDL. OxLDL receptor LOX-1 showed a maximum induction after 7 hours. Increased LOX-1 protein expression in response to oxLDL could be blocked by a LOX-1 specific antibody. TLR4 expression was increased by nLDL and oxLDL as well. We conclude that LDL and oxLDL can activate the renin-angiotensin system and their receptors LDLR, LOX-1, and TLR4 in human endothelial cells. These data suggest a novel link between hypercholesterolemia and hypertension in patients with the metabolic syndrome.