Zhang Congcong, Li Yulin, Wang Chunxiao, Wu Yina, Du Jie
Beijing AnZhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
Am J Hypertens. 2014 Jun;27(6):857-64. doi: 10.1093/ajh/hpt274. Epub 2014 Jan 13.
Inflammatory 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.
Hypertension 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 1mg/kg, intraperitoneally 1 day before and daily during Ang II infusion.
Although 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 β1 (TGF-β1) 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.
Our data suggest that inhibition of C5aR could be a potential therapeutic strategy in preventing organ damage in Ang II-induced hypertension.
炎症反应介导高血压所致的血管周围纤维化和心脏功能障碍的发展。补体是一个重要的炎症系统，我们旨在评估特异性C5a受体拮抗剂（C5aRA）PMX53对小鼠高血压心脏炎症和血管周围纤维化的影响。
通过以1500 ng/kg/分钟的剂量皮下输注血管紧张素II（Ang II）7天来诱导高血压。在Ang II输注前1天腹腔注射剂量为1mg/kg的PMX53，并在Ang II输注期间每天注射。
尽管C5aRA治疗不影响Ang II输注所致的血压升高，但它减轻了心肌细胞肥大、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β1（TGF-β1）和结缔组织生长因子（CTGF）的mRNA和蛋白水平在Ang II输注后也被C5aRA治疗所减弱。
我们的数据表明，抑制C5aR可能是预防Ang II诱导的高血压中器官损伤的一种潜在治疗策略。
