Background Atherosclerosis in humans and mice has inflammatory, immune and metabolic components. Mice lacking low-density lipoprotein receptor (LDLR(−/−)) may be protected from atherogenesis by some components of the complement system. The serum glycoprotein Properdin is a key amplifier of complement activation. The role of Properdin in atherosclerosis has not yet been studied.

Methodology We crossed LDLR(−/−) mice with Properdin-knockout mice and examined atherosclerosis in LDLR(−/−) Properdin-knockout (LDLR(−/−)P-KO) mice compared with LDLR(−/−) Properdin-wildtype (LDLR(−/−)P-WT) fed either a low (LFD) or high-fat diet (HFD; Abdiets / The Netherlands) for 12 weeks.

Results On LFD, there were no differences in body weight, atherosclerotic burden in aortae and lipid profiles between genotypes (LDLR(−/−)P-KO vs LDLR(−/−)P-WT) or genders. This was not the case in mice fed the HFD. On HFD, % lesion coverage in the aorta was greater in female LDLR(−/−)P-KO mice compared with males (5.06±0.71 % (f) vs 1.44±0.16 % (m), p<0.005, n=4). There was also a greater per cent increase in body weight in female LDLR(−/−)P-KO mice (14.45±1.31 % (f) vs 5.03±2.13 % (m), p<0.01, n=4). Total cholesterol was also 2.4-fold greater in LDLR(−/−)P-KO females than in LDLR(−/−)P-KO males on HFD (1698±44 mg/dl (f) vs 699±188 mg/dl (m), p<0.005, n=4).

Conclusion These data provide preliminary evidence that Properdin may be protective in HFD-induced atherosclerosis in female mice and the mechanism for this observation is currently under investigation.