Complement C5a receptor inhibition reduces atherosclerosis in ApoE-/- mice.

Helga Manthey, Anita C Thomas, Ian Shiels, Alma Zerneke, Trent Woodruff, Barbara Rolfe, Stephen Taylor

Research output: Contribution to journalArticle (Academic Journal)peer-review


The complement C5a receptor, CD88, is present on many of the cells found within human atherosclerotic plaques, but little is known about the role of C5a in atherogenesis. Using real-time PCR, we determined that ApoE(-/-) mice fed a normal diet express more aortic CD88 mRNA compared with controls, and this increase coincides with atherosclerotic lesion development (P<0.001 for 3- vs. 25-wk-old animals). Conversely, mRNA expression of the alternative C5a receptor, C5L2, in aortas of ApoE(-/-) mice, was lower than controls at all time points. Using immunohistochemistry, we confirmed the presence of CD88 on macrophages, smooth muscle cells, and activated endothelial cells in plaques from brachiocephalic arteries. Treatment of ApoE(-/-) mice with a CD88 antagonist (PMX53; 3 mg/kg s.c. 3 x/wk plus 1 mg/kg/d p.o.) for 25 wk reduced lesion size and lipid content in the plaque by approximately 40% (P<0.05). Our study provides evidence for a proatherogenic role for C5a and identifies the CD88 antagonist PMX53 as a potential antiatherosclerotic drug
Original languageEnglish
Pages (from-to)2447-2455
Number of pages9
JournalFASEB Journal
Publication statusPublished - 2011


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