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. I n the present study, we focused on class A scavenger receptor (SR-A) activi ty and ApoE expression in macrophages from both rabbit strains. These param eters play a crucial role in maintaining cholesterol homeostasis in the art erial wall and may be involved in the development of atherosclerosis. SR ac tivity, as measured by uptake of DiI-labeled acetylated LDL, was significan tly 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 h igher SR activity was caused by a greater number of SRs (apparent V-max, 41 00 ng/mg in LAR and 1980 ng/mg in HAR rabbits), The high SR activity in mac rophages from LAR rabbits was associated with a significantly higher expres sion of SR-A mRNA compared with macrophages from HAR rabbits. However, the latter finding could not be explained by differences in the activity of tra nscription factor-activating protein 1 (AP-1), which was comparable in macr ophages from both strains of rabbits. Because under certain circumstances S R-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 presenc e of adequate amounts of ApoE may play a role in attenuating atherosclerosi s in LAR rabbits.