Abstract 1205: Scavenger Receptor CD36 has a Role in HDL Metabolism in Mice
Background: Scavenger receptor CD36 binds HDL particles but mediates selective HDL Cholesteryl Ester (CE) uptake in vitro at low rates. The role of CD36 in HDL metabolism in mice was explored.
Methods: Male wildtype (WT) mice and mice with a targeted mutation in the CD36 gene (knockout, KO, homozygous) were the model. Murine WT HDL was doubly radiolabeled with 125I-TC (protein) and [3H]Cholesteryl Oleyl Ether ([3H]CEt) (CE) and finally injected in both groups of mice. During a 24 hour period, blood was drawn periodically for tracer decay analysis and calculation of plasma fractional catabolic rates (plasma-FCR’s). Finally the animals were sacrified and tracer content of 10 organs was analyzed for calculation of organ tracer uptake rates (organ-FCR’s).
Results: Plasma cholesterol was 89.2 mg/dl (WT) and 119.0 (CD36 KO) in mice (n = 27 per group, p = 0.001). This increase in total cholesterol was due to a rise of HDL cholesterol in CD36 KO mice. Plasma-FCR’s for HDL-associated [3H]CEt were higher than those for 125I-TC demonstrating selective HDL CE removal from the circulation. Plasma-FCR’s for [3H]CEt and 125I-TC were lower in CD36 KO mice compared to WT. The difference between HDL plasma-FCR’s for [3H]CEt and 125I-TC yields selective HDL CE removal from plasma and the respective rates were decreased in CD36 KO mice compared to WT (WT 0.088 pools per hour, CD36 KO 0.053, n = 5 mice, p = 0.002). Liver organ-FCR’s for HDL-associated [3H]CEt were higher than those for 125I-TC showing selective HDL CE uptake. Hepatic organ-FCR’s for [3H]CEt and 125I-TC decreased in CD36 KO mice compared to WT. The difference in liver organ-FCR’s between [3H]CEt and 125I-TC yields hepatic selective HDL CE uptake and this rate decreased in CD36 KO mice (WT 0.0766 pools per hour, CD36 KO 0.0435, n = 5 mice, p = 0.001). Expression of scavenger receptor BI (SR-BI) in the liver of WT and CD36 KO mice was explored in immunoblots. SR-BI expression was similar in WT and in CD36 KO murine liver.
Conclusions: In mice, a lack of CD36 expression increases plasma total and HDL cholesterol significantly. Besides, a CD36 deficiency decreases HDL catabolism and reduces selective HDL CE uptake by the liver substantially. Thus scavenger receptor CD36 plays an important role in HDL metabolism in mice.