Characterization of cholesterol loading effect on the gene expression of bone marrow derived macrophages of AKR and DBA/2 ApoE-deficient mice. Mus musculus

Strain effects on the response to cholesterol loading in bone marrow derived macrophages (BMM) are not well studied. The atherosclerosis susceptible strain, DBA/2 on the ApoE deficient background and the atherosclerosis resistant AKR strains show differences in cholesterol handling when loaded with AcLDL. To understand the molecular basis for these differences, BMM from both strains were loaded with acetylated low desnisty lipoprotein (AcLDL) and gene expression quantified. BMMs from AKR greatly upregulated transcripts involved in the lysosomal trafficking pathway. This experiment strongly suggest that upregualtion of the lysosomal pathway in response to AcLDL maybe protective against atherosclerosis. In addition we find that transcripts containing the sterol response element (SRE) motif had strong strain-loading interactions suggesting a strain response to SRE response. Overall design: 32 BMM cultures from AKR (n=16) and DBA/2 (n=16) mice of both genders (16 males and 16 females) were loaded with AcLDL (n=16) or control media (n=16) resulting in 4 biological replicates for each of the conditions, gender, loading, and strain.