Rabbit atherosclerotic lesions express scavenger receptor AIII mRNA, a naturally occurring splice variant that encodes a non-functional, dominant negative form of the macrophage scavenger receptor

Macrophage class A scavenger receptor types I and II (SR-AI and II) mediate the uptake of oxidized LDL in atherosclerotic lesions. The recently descri bed type III receptor (SR-AIII), which lacks amino acids encoded by exon 10 of the SR-A gene. is unable to mediate the uptake of ligands and acts as a dominant negative regulator in the trimeric SR-A molecule. To find out whe ther SR-AIII might play a role in the regulation of SR-A activity in the ar terial wall, we studied its expression in normal and atherosclerotic aortic intima-medias of Watanabe heritable hyperlipidemic (WHHL) and cholesterol- fed New Zealand white (NZW) rabbits. SR-A mRNA was amplified by reverse tra nscription-polymerase chain reaction (RT-PCR) with a SR-AIII-specific prime r pair and with a primer pair suitable for both SR-AI and III. Very low SR- AI expression and no SR-AIII expression was found in the lesion-free aortic intima-medias of WHHL rabbits and control NZW rabbits. WHHL rabbit fatty s treaks contained abundant SR-AI expression and low-level SR-AIII expression . In contrast. the numerous fatty streaks and fatty plaques appearing in th e aortas of cholesterol-fed (14 weeks) NZW rabbits, and the fatty plaques o f WHHL rabbits contained clearly detectable SR-AIII expression in addition to the abundant SR-AI expression. In addition, SR-AIII mRNA was detected in NZW and WHHL rabbit livers. The results suggest that in advanced atheroscl erotic lesions, cells may protect themselves from the excessive uptake of o xidized lipoproteins by generating SR-A molecules which cannot bind modifie d LDL. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.