Scavenger receptor SR-BI has been implicated in HDL-dependent atheroprotective mechanisms. We report the generation of an SR-BI conditional knockout mouse model in which SR-BI gene targeting by loxP site insertion produced a hypomorphic allele (hypomSR-BI). Attenuated SR-BI expression in hypomSR-BI mice resulted in 2-fold elevation in plasma total cholesterol (TC) levels. Cre-mediated SR-BI gene inactivation of the hypomorphic SR-BI allele in hepatocytes (hypomSR-BI-KO liver ) was associated with high plasma TC concentrations, increased plasma free cholesterol/TC (FC/TC) ratio, and a lipoprotein-cholesterol profile typical of SR-BI -/-mice. Plasma TC levels were increased 2-fold in hypomSR-BI and control mice fed an atherogenic diet, whereas hypomSR-BI-KO liver and SR-BI -/-mice developed severe hypercholesterolemia due to accumulation of FC-rich, VLDL-sized particles. Atherosclerosis in hypomSR-BI mice was enhanced (2.5-fold) compared with that in controls, but to a much lower degree than in hypomSR-BI-KO liver (32-fold) and SR-BI -/-(48-fold) mice. The latter models did not differ in either plasma lipid levels or in the capacity of VLDL-sized lipoproteins to induce macrophage cholesterol loading. However, reduced atherosclerosis in hypomSR-BI-KO liver mice was associated with decreased lesional macrophage content as compared with that in SR-BI -/-mice. These data imply that, in addition to its major atheroprotective role in liver, SR-BI may exert an antiatherogenic role in extrahepatic tissues.

1. Four groups of rats were fed for 49 d on one of four semi-purified diets, without added cholesterol and containing 230 g/kg of the following isolated proteins: casein, whey, soya-bean or sunflower.2. Whey, soya-bean and sunflower proteins, when compared with casein, decreased the level of serum high-density-lipoprotein (HDL)-cholesterol. These low cholesterol levels were accompanied by an increase in the daily faecal excretion of neutral sterols and bile acids in the case of soya-bean protein, and by a decrease in the liver cholesterol content, when rats were fed on whey protein.3. Considering the amino acid composition of the four purified proteins, we observed that serum total and HDL-cholesterol levels had a significant positive correlation with tyrosine and glutamic acid, and a negative correlation with cystine and alanine.4. The present study showed that the hypocholesterolaemic effect of dietary proteins was not related to their animal or vegetable origin.

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