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
This article has been cited by other articles:
 |
|
 |
|
  J. Sendra, V. Llorente-Cortes, P. Costales, C. Huesca-Gomez, and L. Badimon Angiotensin II upregulates LDL receptor-related protein (LRP1) expression in the vascular wall: a new pro-atherogenic mechanism of hypertension Cardiovasc Res, June 1, 2008; 78(3): 581 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Crawford, A. S. Nord, M. D. Badzioch, J. Ranchalis, L. A. McKinstry, M. Ahearn, C. Bertucci, C. Shephard, M. Wong, M. J. Rieder, et al. A common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk J. Lipid Res., March 1, 2008; 49(3): 588 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Nikolic, M. C. Gong, J. Turk, and S. R. Post Class A Scavenger Receptor-mediated Macrophage Adhesion Requires Coupling of Calcium-independent Phospholipase A2 and 12/15-Lipoxygenase to Rac and Cdc42 Activation J. Biol. Chem., November 16, 2007; 282(46): 33405 - 33411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Llorente-Cortes, T. Royo, M. Otero-Vinas, M. Berrozpe, and L. Badimon Sterol regulatory element binding proteins downregulate LDL receptor-related protein (LRP1) expression and LRP1-mediated aggregated LDL uptake by human macrophages Cardiovasc Res, June 1, 2007; 74(3): 526 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ota, S. Soga, T. Hase, I. Tokimitsu, and T. Murase Dietary Diacylglycerol Induces the Regression of Atherosclerosis in Rabbits J. Nutr., May 1, 2007; 137(5): 1194 - 1199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hernandez-Vargas, G. Ortiz-Munoz, O. Lopez-Franco, Y. Suzuki, J. Gallego-Delgado, G. Sanjuan, A. Lazaro, V. Lopez-Parra, L. Ortega, J. Egido, et al. Fc{gamma} Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout Mice Circ. Res., November 24, 2006; 99(11): 1188 - 1196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bujo and Y. Saito Modulation of Smooth Muscle Cell Migration by Members of the Low-Density Lipoprotein Receptor Family Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1246 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Iwasaki, S. Takahashi, M. Takahashi, Y. Zenimaru, T. Kujiraoka, M. Ishihara, M. Nagano, J. Suzuki, I. Miyamori, H. Naiki, et al. Deficiency of the Very Low-Density Lipoprotein (VLDL) Receptors in Streptozotocin-Induced Diabetic Rats: Insulin Dependency of the VLDL Receptor Endocrinology, August 1, 2005; 146(8): 3286 - 3294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Llorente-Cortes and L. Badimon LDL Receptor-Related Protein and the Vascular Wall: Implications for Atherothrombosis Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 497 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, N. Adhikari, Q. Li, and J. L. Hall LDL receptor-related protein LRP6 regulates proliferation and survival through the Wnt cascade in vascular smooth muscle cells Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2376 - H2383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tanaga, H. Bujo, Y. Zhu, T. Kanaki, S. Hirayama, K. Takahashi, M. Inoue, K. Mikami, W. J. Schneider, and Y. Saito LRP1B Attenuates the Migration of Smooth Muscle Cells by Reducing Membrane Localization of Urokinase and PDGF Receptors Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1422 - 1428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Argmann, C. G. Sawyez, S. Li, Z. Nong, R. A. Hegele, J. G. Pickering, and M. W. Huff Human Smooth Muscle Cell Subpopulations Differentially Accumulate Cholesteryl Ester When Exposed to Native and Oxidized Lipoproteins Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1290 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhu, H. Bujo, H. Yamazaki, K. Ohwaki, M. Jiang, S. Hirayama, T. Kanaki, M. Shibasaki, K. Takahashi, W. J. Schneider, et al. LR11, an LDL Receptor Gene Family Member, Is a Novel Regulator of Smooth Muscle Cell Migration Circ. Res., April 2, 2004; 94(6): 752 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lehtimaki, P. Dastidar, H. Jokela, T. Koivula, S. Lehtinen, C. Ehnholm, and R. Punnonen Effect of Long-Term Hormone Replacement Therapy on Atherosclerosis Progression in Postmenopausal Women Relates to Functional Apolipoprotein E Genotype J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4147 - 4153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Llorente-Cortes, M. Otero-Vinas, E. Hurt-Camejo, J. Martinez-Gonzalez, and L. Badimon Human Coronary Smooth Muscle Cells Internalize Versican-Modified LDL Through LDL Receptor-Related Protein and LDL Receptors Arterioscler Thromb Vasc Biol, March 1, 2002; 22(3): 387 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Taira, H. Bujo, S. Hirayama, H. Yamazaki, T. Kanaki, K. Takahashi, I. Ishii, T. Miida, W. J. Schneider, and Y. Saito LR11, a Mosaic LDL Receptor Family Member, Mediates the Uptake of ApoE-Rich Lipoproteins In Vitro Arterioscler Thromb Vasc Biol, September 1, 2001; 21(9): 1501 - 1506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kosaka, S. Takahashi, K. Masamura, H. Kanehara, J. Sakai, G. Tohda, E. Okada, K. Oida, T. Iwasaki, H. Hattori, et al. Evidence of Macrophage Foam Cell Formation by Very Low-Density Lipoprotein Receptor : Interferon-{{gamma}} Inhibition of Very Low-Density Lipoprotein Receptor Expression and Foam Cell Formation in Macrophages Circulation, February 27, 2001; 103(8): 1142 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. R. Babaev, L. A. Gleaves, K. J. Carter, H. Suzuki, T. Kodama, S. Fazio, and M. F. Linton Reduced Atherosclerotic Lesions in Mice Deficient for Total or Macrophage-Specific Expression of Scavenger Receptor-A Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2593 - 2599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Van Eck, M. P. J. De Winther, N. Herijgers, L. M. Havekes, M. H. Hofker, P. H. E. Groot, and T. J. C. Van Berkel Effect of Human Scavenger Receptor Class A Overexpression in Bone Marrow-Derived Cells on Cholesterol Levels and Atherosclerosis in ApoE-Deficient Mice Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2600 - 2606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Herijgers, M. P. J. de Winther, M. Van Eck, L. M. Havekes, M. H. Hofker, P. M. Hoogerbrugge, and T. J. C. Van Berkel Effect of human scavenger receptor class A overexpression in bone marrow-derived cells on lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knockout mice J. Lipid Res., September 1, 2000; 41(9): 1402 - 1409. [Abstract] [Full Text]
|
|
|
|
|
|
V. Terpstra, E. S. van Amersfoort, A. G. van Velzen, J. Kuiper, and T. J. C. van Berkel Hepatic and Extrahepatic Scavenger Receptors : Function in Relation to Disease Arterioscler Thromb Vasc Biol, August 1, 2000; 20(8): 1860 - 1872. [Full Text] [PDF]
|
|
|
|
|
|
Bjorn Lundahl, T. P. Leren, L. Ose, A. Hamsten, and F. Karpe A Functional Polymorphism in the Promoter Region of the Microsomal Triglyceride Transfer Protein (MTP -493G/T) Influences Lipoprotein Phenotype in Familial Hypercholesterolemia Arterioscler Thromb Vasc Biol, July 1, 2000; 20(7): 1784 - 1788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Llorente-Cortes, J. Martinez-Gonzalez, and L. Badimon LDL Receptor-Related Protein Mediates Uptake of Aggregated LDL in Human Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1572 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Laukkanen, P. Lehtolainen, P. J. Gough, D. R. Greaves, S. Gordon, and S. Yla-Herttuala Adenovirus-Mediated Gene Transfer of a Secreted Form of Human Macrophage Scavenger Receptor Inhibits Modified Low-Density Lipoprotein Degradation and Foam-Cell Formation in Macrophages Circulation, March 14, 2000; 101(10): 1091 - 1096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lehtolainen, M. Takeya, and S. Yla-Herttuala Retrovirus-Mediated, Stable Scavenger-Receptor Gene Transfer Leads to Functional Endocytotic Receptor Expression, Foam Cell Formation, and Increased Susceptibility to Apoptosis in Rabbit Aortic Smooth Muscle Cells Arterioscler Thromb Vasc Biol, January 1, 2000; 20(1): 52 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kanaki, H. Bujo, S. Hirayama, I. Ishii, N. Morisaki, W. J. Schneider, and Y. Saito Expression of LR11, a Mosaic LDL Receptor Family Member, Is Markedly Increased in Atherosclerotic Lesions Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2687 - 2695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Whitman, C. A. Argmann, C. G. Sawyez, D. B. Miller, R. A. Hegele, and M. W. Huff Uptake of type IV hypertriglyceridemic VLDL by cultured macrophages is enhanced by interferon-{gamma} J. Lipid Res., June 1, 1999; 40(6): 1017 - 1028. [Abstract] [Full Text]
|
|
|
|
|
|
L. Nilsson, M. Gåfvels, L. Musakka, K. Ensler, D. K. Strickland, B. Angelin, A. Hamsten, and P. Eriksson VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor J. Lipid Res., May 1, 1999; 40(5): 913 - 919. [Abstract] [Full Text]
|
|
|
|
|
|
P. J. Gough, D. R. Greaves, H. Suzuki, T. Hakkinen, M. O. Hiltunen, M. Turunen, S. Y. Herttuala, T. Kodama, and S. Gordon Analysis of Macrophage Scavenger Receptor (SR-A) Expression in Human Aortic Atherosclerotic Lesions Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 461 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. de Vries, B. Buchner, T. J. C. van Berkel, and J. Kuiper Specific Interaction of Oxidized Low-Density Lipoprotein With Macrophage-Derived Foam Cells Isolated From Rabbit Atherosclerotic Lesions Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 638 - 645. [Abstract] [Full Text] [PDF]
|
|