Department of Cardiovascular surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, China.
Department of Cardiovascular surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, China.
Biomed Pharmacother. 2018 Oct;106:1448-1453. doi: 10.1016/j.biopha.2018.07.025. Epub 2018 Jul 24.
Oxidized LDL (ox-LDL) is one of the major risk factors of atherosclerosis. Endothelial dysfunction caused by ox-LDL is an early event in the pathogenesis of cardiovascular diseases. Preclinical studies have been performed to explore efficient means of preventing endothelial abnormalities. In this study, we revealed that loratadine, a histamine H1 type receptor specific antagonist, possesses a protective effect by relieving ox-LDL-induced endothelial inflammation. Treatment of endothelial cells with ox-LDL induces expression of the H1 receptor. The presence of loratadine in endothelial culture efficiently suppressed ox-LDL-induced attachment of monocytes to endothelial cells, production of ROS and vascular adhesion molecules, and induction cytokines including VCAM-1, E-selectin, TNF-α, IL-6 and IL-8. Mechanistically, we show that loratadine potently blocks ox-LDL-induced JNK activation as well as the AP-1 and NF-κB signaling pathways. Collectively, our data disclose a new role for loratadine in endothelial protection.
氧化型低密度脂蛋白(ox-LDL)是动脉粥样硬化的主要危险因素之一。ox-LDL 引起的内皮功能障碍是心血管疾病发病机制中的早期事件。已经进行了临床前研究以探索预防内皮异常的有效方法。在这项研究中,我们揭示了氯雷他定(一种组胺 H1 型受体特异性拮抗剂)通过缓解 ox-LDL 诱导的内皮炎症具有保护作用。ox-LDL 处理内皮细胞可诱导 H1 受体的表达。内皮细胞培养物中存在氯雷他定可有效抑制 ox-LDL 诱导的单核细胞附着在内皮细胞上、ROS 和血管黏附分子的产生以及细胞因子的诱导,包括 VCAM-1、E-选择素、TNF-α、IL-6 和 IL-8。从机制上讲,我们表明氯雷他定能够强烈阻断 ox-LDL 诱导的 JNK 激活以及 AP-1 和 NF-κB 信号通路。总之,我们的数据揭示了氯雷他定在保护内皮中的新作用。