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 described 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 whether SR-AIII might play a role in the regulation of SR-A activity in the arterial 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 transcription-polymerase chain reaction (RT-PCR) with a SR-AIII-specific primer 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 streaks contained abundant SR-AI expression and low-level SR-AIII expression. In contrast, the numerous fatty streaks and fatty plaques appearing in the aortas of cholesterol-fed (14 weeks) NZW rabbits, and the fatty plaques of 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 atherosclerotic lesions, cells may protect themselves from the excessive uptake of oxidized lipoproteins by generating SR-A molecules which cannot bind modified LDL.
Hiltunen
T P
TP
Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Gough
P J
PJ
Greaves
D R
DR
Gordon
S
S
Ylä-Herttuala
S
S
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000633:toxicity; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D008297:Male; D008565:Membrane Proteins; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
D015815:Cell Adhesion Molecules; D002791:Cholesterol, Dietary; D017931:DNA Primers; D008565:Membrane Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B