Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Oct;90(4):1450–1457. doi: 10.1172/JCI116012

Rabbit aortic smooth muscle cells express inducible macrophage scavenger receptor messenger RNA that is absent from endothelial cells.

P E Bickel 1, M W Freeman 1
PMCID: PMC443191  PMID: 1401078

Abstract

Scavenger receptors mediate uptake of modified low density lipoproteins by macrophages. The accumulation of lipids via this process is thought to lead to foam cell formation in developing atherosclerotic plaques. Smooth muscle cells, which can also be converted to foam cells in vivo, have not been shown to express the same scavenger receptor previously cloned in macrophages. We report the cloning of two cDNAs that encode type I and type II scavenger receptors isolated from rabbit smooth muscle cells. The deduced protein sequences of these isolates are highly homologous to the scavenger receptors previously isolated from macrophages. Treatment of smooth muscle cells with phorbol esters induced a marked increase in scavenger receptor mRNA and a fivefold increase in receptor degradation activity. Rabbit venous endothelial cells in primary culture and a bovine aortic endothelial cell line had no detectable scavenger receptor mRNA, despite having scavenger receptor degradation activity. The latter finding suggests that endothelial cells may possess a scavenger receptor which is structurally distinct from that found in macrophages and smooth muscle cells. The isolation of cDNAs encoding the rabbit scavenger receptor should prove useful for in vitro and in vivo studies that employ the rabbit as a model of human atherosclerosis.

Full text

PDF
1450

Images in this article

1454Image
on p.1454
1454Image
on p.1454
1454Image
on p.1454
1454Image
on p.1454
1454Image
on p.1454
1455Image
on p.1455
1455Image
on p.1455
1455Image
on p.1455
1455Image
on p.1455
1455Image
on p.1455

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arai H., Kita T., Yokode M., Narumiya S., Kawai C. Multiple receptors for modified low density lipoproteins in mouse peritoneal macrophages: different uptake mechanisms for acetylated and oxidized low density lipoproteins. Biochem Biophys Res Commun. 1989 Mar 31;159(3):1375–1382. doi: 10.1016/0006-291x(89)92262-6. [DOI] [PubMed] [Google Scholar]
  2. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  3. Brown M. S., Basu S. K., Falck J. R., Ho Y. K., Goldstein J. L. The scavenger cell pathway for lipoprotein degradation: specificity of the binding site that mediates the uptake of negatively-charged LDL by macrophages. J Supramol Struct. 1980;13(1):67–81. doi: 10.1002/jss.400130107. [DOI] [PubMed] [Google Scholar]
  4. Brown M. S., Goldstein J. L. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem. 1983;52:223–261. doi: 10.1146/annurev.bi.52.070183.001255. [DOI] [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Dresel H. A., Friedrich E., Via D. P., Sinn H., Ziegler R., Schettler G. Binding of acetylated low density lipoprotein and maleylated bovine serum albumin to the rat liver: one or two receptors? EMBO J. 1987 Feb;6(2):319–326. doi: 10.1002/j.1460-2075.1987.tb04757.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Freeman M., Ashkenas J., Rees D. J., Kingsley D. M., Copeland N. G., Jenkins N. A., Krieger M. An ancient, highly conserved family of cysteine-rich protein domains revealed by cloning type I and type II murine macrophage scavenger receptors. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8810–8814. doi: 10.1073/pnas.87.22.8810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Freeman M., Ekkel Y., Rohrer L., Penman M., Freedman N. J., Chisolm G. M., Krieger M. Expression of type I and type II bovine scavenger receptors in Chinese hamster ovary cells: lipid droplet accumulation and nonreciprocal cross competition by acetylated and oxidized low density lipoprotein. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4931–4935. doi: 10.1073/pnas.88.11.4931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goldstein J. L., Ho Y. K., Basu S. K., Brown M. S. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci U S A. 1979 Jan;76(1):333–337. doi: 10.1073/pnas.76.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Higgins D. G., Sharp P. M. Fast and sensitive multiple sequence alignments on a microcomputer. Comput Appl Biosci. 1989 Apr;5(2):151–153. doi: 10.1093/bioinformatics/5.2.151. [DOI] [PubMed] [Google Scholar]
  11. Hu N., Messing J. The making of strand-specific M13 probes. Gene. 1982 Mar;17(3):271–277. doi: 10.1016/0378-1119(82)90143-3. [DOI] [PubMed] [Google Scholar]
  12. Jaakkola O., Kallioniemi O. P., Nikkari T. Lipoprotein metabolism of human and rabbit arterial cells in primary culture. Eur Heart J. 1990 Aug;11 (Suppl E):128–133. doi: 10.1093/eurheartj/11.suppl_e.128. [DOI] [PubMed] [Google Scholar]
  13. Jaakkola O., Nikkari T. Lipoprotein degradation and cholesterol esterification in primary cell cultures of rabbit atherosclerotic lesions. Am J Pathol. 1990 Aug;137(2):457–465. [PMC free article] [PubMed] [Google Scholar]
  14. Kodama T., Freeman M., Rohrer L., Zabrecky J., Matsudaira P., Krieger M. Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature. 1990 Feb 8;343(6258):531–535. doi: 10.1038/343531a0. [DOI] [PubMed] [Google Scholar]
  15. Krieger M. Complementation of mutations in the LDL pathway of receptor-mediated endocytosis by cocultivation of LDL receptor-defective hamster cell mutants. Cell. 1983 Jun;33(2):413–422. doi: 10.1016/0092-8674(83)90423-3. [DOI] [PubMed] [Google Scholar]
  16. Kume N., Arai H., Kawai C., Kita T. Receptors for modified low-density lipoproteins on human endothelial cells: different recognition for acetylated low-density lipoprotein and oxidized low-density lipoprotein. Biochim Biophys Acta. 1991 Jan 10;1091(1):63–67. doi: 10.1016/0167-4889(91)90223-k. [DOI] [PubMed] [Google Scholar]
  17. Masuda J., Ross R. Atherogenesis during low level hypercholesterolemia in the nonhuman primate. I. Fatty streak formation. Arteriosclerosis. 1990 Mar-Apr;10(2):164–177. doi: 10.1161/01.atv.10.2.164. [DOI] [PubMed] [Google Scholar]
  18. Matsumoto A., Naito M., Itakura H., Ikemoto S., Asaoka H., Hayakawa I., Kanamori H., Aburatani H., Takaku F., Suzuki H. Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9133–9137. doi: 10.1073/pnas.87.23.9133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nabel E. G., Plautz G., Nabel G. J. Site-specific gene expression in vivo by direct gene transfer into the arterial wall. Science. 1990 Sep 14;249(4974):1285–1288. doi: 10.1126/science.2119055. [DOI] [PubMed] [Google Scholar]
  20. Pitas R. E. Expression of the acetyl low density lipoprotein receptor by rabbit fibroblasts and smooth muscle cells. Up-regulation by phorbol esters. J Biol Chem. 1990 Jul 25;265(21):12722–12727. [PubMed] [Google Scholar]
  21. Rohrer L., Freeman M., Kodama T., Penman M., Krieger M. Coiled-coil fibrous domains mediate ligand binding by macrophage scavenger receptor type II. Nature. 1990 Feb 8;343(6258):570–572. doi: 10.1038/343570a0. [DOI] [PubMed] [Google Scholar]
  22. Rosenfeld M. E., Ross R. Macrophage and smooth muscle cell proliferation in atherosclerotic lesions of WHHL and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis. 1990 Sep-Oct;10(5):680–687. doi: 10.1161/01.atv.10.5.680. [DOI] [PubMed] [Google Scholar]
  23. Seed B., Aruffo A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci U S A. 1987 May;84(10):3365–3369. doi: 10.1073/pnas.84.10.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sparrow C. P., Parthasarathy S., Steinberg D. A macrophage receptor that recognizes oxidized low density lipoprotein but not acetylated low density lipoprotein. J Biol Chem. 1989 Feb 15;264(5):2599–2604. [PubMed] [Google Scholar]
  25. Stary H. C. The sequence of cell and matrix changes in atherosclerotic lesions of coronary arteries in the first forty years of life. Eur Heart J. 1990 Aug;11 (Suppl E):3–19. doi: 10.1093/eurheartj/11.suppl_e.3. [DOI] [PubMed] [Google Scholar]
  26. Stein O., Stein Y. Bovine aortic endothelial cells display macrophage-like properties towards acetylated 125I-labelled low density lipoprotein. Biochim Biophys Acta. 1980 Dec 5;620(3):631–635. doi: 10.1016/0005-2760(80)90155-1. [DOI] [PubMed] [Google Scholar]
  27. Van Berkel T. J., De Rijke Y. B., Kruijt J. K. Different fate in vivo of oxidatively modified low density lipoprotein and acetylated low density lipoprotein in rats. Recognition by various scavenger receptors on Kupffer and endothelial liver cells. J Biol Chem. 1991 Feb 5;266(4):2282–2289. [PubMed] [Google Scholar]
  28. Van Berkel T. J., Nagelkerke J. F., Harkes L., Kruijt J. K. Processing of acetylated human low-density lipoprotein by parenchymal and non-parenchymal liver cells. Involvement of calmodulin? Biochem J. 1982 Nov 15;208(2):493–503. doi: 10.1042/bj2080493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Voyta J. C., Via D. P., Butterfield C. E., Zetter B. R. Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein. J Cell Biol. 1984 Dec;99(6):2034–2040. doi: 10.1083/jcb.99.6.2034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wilson J. M., Birinyi L. K., Salomon R. N., Libby P., Callow A. D., Mulligan R. C. Implantation of vascular grafts lined with genetically modified endothelial cells. Science. 1989 Jun 16;244(4910):1344–1346. doi: 10.1126/science.2734614. [DOI] [PubMed] [Google Scholar]
  31. Wolfbauer G., Glick J. M., Minor L. K., Rothblat G. H. Development of the smooth muscle foam cell: uptake of macrophage lipid inclusions. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7760–7764. doi: 10.1073/pnas.83.20.7760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yablonka-Reuveni Z. The emergence of the endothelial cell lineage in the chick embryo can be detected by uptake of acetylated low density lipoprotein and the presence of a von Willebrand-like factor. Dev Biol. 1989 Mar;132(1):230–240. doi: 10.1016/0012-1606(89)90219-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ylä-Herttuala S., Palinski W., Rosenfeld M. E., Parthasarathy S., Carew T. E., Butler S., Witztum J. L., Steinberg D. Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest. 1989 Oct;84(4):1086–1095. doi: 10.1172/JCI114271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ylä-Herttuala S., Rosenfeld M. E., Parthasarathy S., Sigal E., Särkioja T., Witztum J. L., Steinberg D. Gene expression in macrophage-rich human atherosclerotic lesions. 15-lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts. J Clin Invest. 1991 Apr;87(4):1146–1152. doi: 10.1172/JCI115111. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES