Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
J Immunol Res. 2014;2014:342693. doi: 10.1155/2014/342693. Epub 2014 Nov 30.
Our study intended to prove whether agonistic autoantibodies to angiotensin II type 1 receptor (AT1-AAs) exist in patients with coronary heart disease (CHD) and affect the human endothelial cell (HEC) by upregulating proinflammatory cytokines expression involved in NF-κB pathway. Antibodies were determined by chronotropic responses of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (valsartan and AT1-EC2) as described previously. Interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemotactic protein-1 (MCP-1) expression were improved at both mRNA and protein levels in HEC, while NF-κB in the DNA level was improved detected by electrophoretic mobility shift assays (EMSA). These improvements could be inhibited by specific AT1 receptor blocker valsartan, NF-κB blocker pyrrolidine dithiocarbamate (PDTC), and specific short peptides from the second extracellular loop of AT1 receptor. These results suggested that AT1-AAs, via the AT1 receptor, induce expression of proinflammatory cytokines involved in the activation of NF-κB. AT1-AAs may play a great role in the pathogenesis of the acute coronary syndrome by mediating vascular inflammatory effects involved in the NF-κB pathway.
本研究旨在探讨冠心病患者体内是否存在血管紧张素Ⅱ 1 型受体（AT1）自身抗体（AT1-AAs），以及这些抗体是否通过上调核因子-κB（NF-κB）通路相关的促炎细胞因子表达而影响人内皮细胞（HEC）。通过先前描述的培养乳鼠心肌细胞的变时反应与受体特异性拮抗剂（缬沙坦和 AT1-EC2）耦联来确定抗体。在 HEC 中，白细胞介素-6（IL-6）、血管细胞黏附分子-1（VCAM-1）和单核细胞趋化蛋白-1（MCP-1）的表达在 mRNA 和蛋白水平上均得到改善，而 NF-κB 在 DNA 水平上的改善则通过电泳迁移率变动分析（EMSA）检测到。这些改善可以被 AT1 受体特异性阻滞剂缬沙坦、NF-κB 阻滞剂吡咯烷二硫代氨基甲酸盐（PDTC）以及 AT1 受体第二细胞外环的特异性短肽所抑制。这些结果表明，AT1-AAs 通过 AT1 受体诱导参与 NF-κB 激活的促炎细胞因子表达。AT1-AAs 可能通过介导涉及 NF-κB 通路的血管炎症作用，在急性冠状动脉综合征的发病机制中发挥重要作用。
