Abstract 477: HDL Inhibition of Murine Atherosclerosis Lesion Development is Dependent on Strain Background
Inbred mouse strains vary greatly in their relative atherosensitivity, with C57BL/6 (C57) being the most sensitive and hence the preferred strain for most atherosclerosis studies. Among the resistant strains, FVBN/J (FVB) has been relatively well studied. On the ApoE knockout (E°) background, both mouse strains develop atherosclerotic lesions which are exacerbated by feeding a high fat/high cholesterol western-type diet (WTD). However, the FVB-E° mouse exhibits nearly 10-fold smaller lesions than the C57-E°. Additionally, FVB mice have plasma HDL cholesterol levels that are twice as high as C57. Wild type FVB mice have been shown to have lower inflammatory cell recruitment to the peritoneum upon thioglycollate treatment than C57. Our lab has generated ApoE/ApoA-I double knockout mice (EA°, lacking HDL) on both C57 and FVB background to compare the effect of HDL deficiency on lesion development. We hypothesize that the loss of HDL will have a greater effect on the more lesion susceptible C57 than the resistant FVB.
8 week C57 and FVB E° and EA° mice were kept on a WTD for 6 or 10 weeks and lesions were quantified in the innominate artery, ascending aorta, and aortic root. In all cases mice in the C57 background displayed significantly greater lesion size than mice in the FVB background, except in the ascending aorta of the E° mice at the earlier time point, despite higher plasma cholesterol levels in the FVB mice. The presence of ApoA-I was protective (E° vs EA°) in the C57 strain in the ascending aorta at both time points and its protection became significant in the innominate artery at the 10 week time point. No additional protection was afforded by ApoA-I in the FVB strain. ApoA-I deficiency in FVB mice did not affect inflammatory cell recruitment to the peritoneal cavity or plasma markers of LDL oxidation as greatly as in C57 mice. Plasma monocyte counts both before and after 6 weeks on WTD were higher in C57 mice with no effect of ApoA-I in either strain.
In conclusion, the FVB strain is less sensitive than C57 to lesion development at 3 major arterial sites with no protection afforded by HDL/ApoA-I, whereas HDL/ApoA-I is significantly protective in the C57 strain. This protection may result from the anti-inflammatory/anti-oxidative nature of C57 HDL that is not observed in FVB mice.
- © 2013 by American Heart Association, Inc.