Scavenger receptor activity is increased in macrophages from rabbits with low atherosclerotic response: studies in normocholesterolemic high and low atherosclerotic response rabbits.
We have previously described 2 strains of New Zealand White rabbits with a high (HAR) or low (LAR) atherosclerotic response to hypercholesterolemia. In the present study, we focused on class A scavenger receptor (SR-A) activity and ApoE expression in macrophages from both rabbit strains. These parameters play a crucial role in maintaining cholesterol homeostasis in the arterial wall and may be involved in the development of atherosclerosis. SR activity, as measured by uptake of DiI-labeled acetylated LDL, was significantly higher in macrophages from LAR rabbits (2177+/-253 ng/mg cell protein) than in macrophages from HAR rabbits (1153+/-200 ng/mg cell protein). The higher SR activity was caused by a greater number of SRs (apparent Vmax, 4100 ng/mg in LAR and 1980 ng/mg in HAR rabbits). The high SR activity in macrophages from LAR rabbits was associated with a significantly higher expression of SR-A mRNA compared with macrophages from HAR rabbits. However, the latter finding could not be explained by differences in the activity of transcription factor-activating protein 1 (AP-1), which was comparable in macrophages from both strains of rabbits. Because under certain circumstances SR-A mRNA expression is regulated in parallel with ApoE expression, we also evaluated this parameter. Although ApoE mRNA was 74% higher in macrophages from LAR rabbits, the difference did not reach statistical significance. In conclusion, the increased expression of SR-A in macrophages in the presence of adequate amounts of ApoE may play a role in attenuating atherosclerosis in LAR rabbits.
D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis* / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000378:metabolism; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007178:Inbreeding; D008077:Lipoproteins, LDL / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D014158:Transcription, Genetic