From the Department of Medical Biochemistry, University of Tampere
Medical School (T.P.H., T.N.); the Department of Clinical Chemistry, Tampere
University Hospital (T.P.H.); and the A.I. Virtanen Institute (J.S.L.,
S.Y.-H.) and Department of Medicine (S.Y.-H.), University of Kuopio, Finland.
Correspondence to Seppo Ylä-Herttuala, MD, PhD, A.I. Virtanen Institute, University of Kuopio, PO Box 1627, Neulaniementie 2, FIN-70211 Kuopio, Finland. E-mail ylahertt{at}keula.uku.fi
Background—Atherosclerotic lesions
contain foam cells that arise from monocyte-macrophages and
smooth muscle cells (SMCs) by excessive uptake of lipoproteins. There
are many candidate receptors for the lipid accumulation, such as LDL
receptor (LDLR), VLDL receptor (VLDLR), LDL receptor-related protein
(LRP), and scavenger receptors (SRs). However, little quantitative
information exists on the expression of these receptors in normal and
atherosclerotic arteries.
Methods and Results—Competitive reverse transcription–polymerase
chain reaction and in situ hybridization were used for the studies in
New Zealand White (NZW) and Watanabe heritable
hyperlipidemic (WHHL) rabbit aortic intima-medias. NZW
rabbits were fed a 1% cholesterol diet for 0 (control
group), 3, 6, or 14 weeks. LDLR mRNA expression was low in aortic
intima-medias of all groups. Of the analyzed receptors, LRP had
the highest expression in the control group, and its mRNA was induced
threefold in the 14-week group, the aortas of which had extensive
lesions. SR expression was low and VLDLR expression moderate in the
control group. Both receptors were highly induced during
cholesterol feeding (SRs, 3-fold and 270-fold induction;
VLDLR, 15-fold and 100-fold induction in the 3-week and 14-week groups,
respectively). Comparable results were obtained from WHHL rabbits: high
basal LRP mRNA in normal intima-medias; moderate induction of LRP and
marked induction of SRs and VLDLR in fatty streaks and fatty plaques.
In situ hybridization indicated that LRP and VLDLR were expressed in
SMCs and macrophages. VLDLR expression was also observed in
endothelial cells. SR expression was detected only in
macrophages.
Conclusions—SR and VLDLR mRNAs were highly induced in
atherosclerotic lesions. VLDLR and LRP may be involved in the formation
of both SMC–and macrophage-derived foam cells, whereas SRs
play an important role in lipid uptake in macrophages.
© 1998 American Heart Association, Inc.
Basic Science Reports
Expression of LDL Receptor, VLDL Receptor, LDL Receptor–Related Protein, and Scavenger Receptor in Rabbit Atherosclerotic Lesions
Marked Induction of Scavenger Receptor and VLDL Receptor Expression During Lesion Development
Key Words: proteins • lipoproteins • atherosclerosis • receptors
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