© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Scavenger Receptor Activity Is Increased in Macrophages From Rabbits With Low Atherosclerotic Response:
Studies in Normocholesterolemic High and Low Atherosclerotic Response Rabbits
From the Institute of Clinical Chemistry, University Hospital Grosshadern (D.T., R.B., J.T.), Munich, Germany; the Lipid Research Laboratory (O.S., Y.S.), Division of Medicine, Hadassah University Hospital, Jerusalem, Israel; and the Department of Experimental Animal Research (K.N.), University Hospital Göttingen, Göttingen, Germany.
Correspondence to Joachim Thiery Institute for Clinical Chemistry, University Hospital Grosshadern, Marchioninistrasse 15, 81366 Munich, Germany. E-mail thiery{at}klch.med.uni-muenchen.de
Abstract—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.
Key Words: atherosclerosis • scavenger receptor • ApoE • hypercholesterolemia • rabbit macrophages
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