Abstract 1389: The Association Of Scavenger Receptor Class B Type I (SR-BI) Protein With HDL-C Levels In Humans With Hyperalphalipoproteinemia
In mice, deficiency of scavenger receptor class B type I (SR-BI) is associated with increased HDL-C levels. However, the relationship of SR-BI with HDL-C levels in humans is still unclear. Therefore, community-dwelling adult subjects between the ages of 18 – 80 years with HDL-C levels ≥ 60 mg/dl were recruited for this on-going prospective study. After an overnight fast, blood was obtained for the purposes of isolating monocytes (which were differentiated to macrophages within 10 days of culture and used for SR-BI protein measurements by western blotting) and plasma for lipid and lipoprotein NMR spectroscopy (Liposcience, NC) measurements. Macrophage SR-BI protein levels were significantly inversely correlated with HDL-C levels (Spearman’s correlation −0.31, p=0.05, n=41). When the distribution of SR-BI protein levels was classified as low (<25th percentile, HDL 102.4 ± 7.0 mg/dl), intermediate (between the 25th and 75th percentiles, HDL 92.5 ± 4.9 mg/dl) or high (>75th percentile, 80.8 ± 6.6 mg/dl), HDL-C levels increased significantly as SR-BI protein levels decreased (p=0.05 comparing high to low). The size of HDL particles were also significantly inversely correlated with SR-BI protein levels (Pearson’s correlation r= −0.31, p=0.05), whereas CE-uptake from HDL was significantly directly correlated with SR-BI protein levels (Pearson’s correlation r=0.40, p=0.03, n=29). We next examined the independent effect of SR-BI protein on HDL-C levels. We considered age, gender, body mass index, smoking, alcohol use, exercise, hormone replacement therapy, triglycerides, hemoglobin A1C, fish oil use and SR-BI protein levels as predictors of HDL-C levels in a multiple regression analysis using a stepwise selection procedure. A model accounting for 56% of the variation in HDL-C levels (model p<0.0001) retained gender, smoking, hemoglobin A1C, triglycerides, and SR-BI protein levels. Gender (p=0.0005), triglyceride levels (p=0.01), and SR-BI protein levels (p=0.01) were significant independent predictors of HDL-C levels. Thus, in subjects with hyperalphalipoproteinemia, SR-BI protein levels were inversely associated with HDL-C levels and HDL size and significantly predicted HDL-C levels independently of gender and other covariates.