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Congcong Zhang, Yulin Li, Chunxiao Wang, Yina Wu, Jie Du, Antagonist of C5aR Prevents Cardiac Remodeling in Angiotensin II–Induced Hypertension, American Journal of Hypertension, Volume 27, Issue 6, June 2014, Pages 857–864, https://doi.org/10.1093/ajh/hpt274
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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.