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.
Statistics from Altmetric.com
Funding This study is supported by the British Heart Foundation (Grant No PG/09/053/27836).
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.