Antagonist of C5aR Prevents Cardiac Remodeling in Angiotensin II-Induced Hypertension
Antagonist of C5aR Prevents Cardiac Remodeling in Angiotensin II-Induced Hypertension
复制标题
C5aR 拮抗剂可预防血管紧张素 II 诱发的高血压中的心脏重塑
DOI：
10.1093/ajh/hpt274
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发表时间：
2014-06-01
影响因子：
3.2
通讯作者：
Du, Jie
中科院分区：
文献类型：
--
作者：
Zhang, Congcong;Li, Yulin;Du, Jie
炎症反应介导高血压引起的血管周围纤维化和心功能障碍的发展。补体是一个重要的炎症系统，我们的目的是评估一种特异性的C5 a受体拮抗剂（C5 aRA），PMX 53，对炎症和血管周围纤维化的影响在高血压小鼠的heart.MethodsHypertension诱导血管紧张素II（Ang II）在皮下注射剂量为1500 ng/kg/min的7天。在Ang II输注前1天和输注期间每天腹腔内给予PMX 53 1 mg/kg。C5 aRA治疗虽然不影响由Ang II输注引起的血压升高，但它减少了心肌细胞肥大、心脏炎症和血管周围纤维化。通过实时聚合酶链反应和免疫组织化学染色测量，促纤维化细胞因子转化生长因子β 1（TGF-β 1）和结缔组织生长因子（CTGF）的mRNA和蛋白水平也通过C5 aRA治疗而减弱。Ang II输注后。结论我们的数据表明，抑制C5 aR可能是预防Ang II诱导的高血压器官损伤的潜在治疗策略。
BACKGROUNDInflammatory responses mediate the development of perivascular fibrosis and heart dysfunction induced by hypertension. Complement is an important inflammatory system, and we aimed to evaluate the effect of a specific C5a receptor antagonist (C5aRA), PMX53, on inflammation and perivascular fibrosis in the hypertensive heart of the mouse.METHODSHypertension was induced by angiotensin II (Ang II) subcutaneously infused at a dose of 1500 ng/kg/min for 7 days. PMX53 was administrated at a dose of 1 mg/kg, intraperitoneally 1 day before and daily during Ang II infusion.RESULTSAlthough C5aRA treatment did not affect the elevated blood pressure by Ang II infusion, it reduced cardiomyocyte hypertrophy, cardiac inflammation, and perivascular fibrosis. The mRNA and protein levels of the profibrotic cytokines transforming growth factor beta 1 (TGF-beta 1) and connective tissue growth factor (CTGF), as measured by real-time polymerase chain reaction and immunohistochemistry staining, were also attenuated by C5aRA treatment after Ang II infusion.CONCLUSIONSOur data suggest that inhibition of C5aR could be a potential therapeutic strategy in preventing organ damage in Ang II-induced hypertension.