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. 1978 Jan;75(1):356–360. doi: 10.1073/pnas.75.1.356

Role of contact inhibition in the regulation of receptor-mediated uptake of low density lipoprotein in cultured vascular endothelial cells.

I Vlodavsky, P E Fielding, C J Fielding, D Gospodarowicz
PMCID: PMC411247  PMID: 203937

Abstract

Bovine vascular endothelial cells during logarithmic growth bind, internalize, and degrade low density lipoprotein (LDL) via a receptor-mediated pathway. However, contact-inhibited (confluent) monolayers bind but do not internalize LDL. This is in contrast to aortic smooth muscle cells or endothelial cells that have lost the property of contact inhibition. These cells internalize and degrade LDL at both high and low cell densities. The LDL receptors of smooth muscle and sparse endothelial cells down-regulate in response to LDL. In contrast, normal endothelial cells at confluency show little response. When contact inhibition in endothelial monolayers was locally released by wounding, and LDL was present, only cells released from contact inhibition accumulated LDL cholesterol. In smooth muscle cells under the same conditions, the entire culture interiorized lipid. It thus appears that in endothelial cells, unlike smooth muscle cells, contact inhibition is the major factor regulating cellular uptake of LDL cholesteryl ester. Reversal of contact inhibition by wounding provides a mechanism by which the endothelium could be the primary initiator of the atherosclerotic plaque.

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Selected References

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  1. Anderson R. G., Brown M. S., Goldstein J. L. Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts. Cell. 1977 Mar;10(3):351–364. doi: 10.1016/0092-8674(77)90022-8. [DOI] [PubMed] [Google Scholar]
  2. Bierman E. L., Stein O., Stein Y. Lipoprotein uptake and metabolism by rat aortic smooth muscle cells in tissue culture. Circ Res. 1974 Jul;35(1):136–150. doi: 10.1161/01.res.35.1.136. [DOI] [PubMed] [Google Scholar]
  3. GILBY A. R. Lutein in a bacterial membrane. Nature. 1958 Jul 5;182(4627):55–56. doi: 10.1038/182055a0. [DOI] [PubMed] [Google Scholar]
  4. Goldstein J. L., Anderson R. G., Buja L. M., Basu S. K., Brown M. S. Overloading human aortic smooth muscle cells with low density lipoprotein-cholesteryl esters reproduces features of atherosclerosis in vitro. J Clin Invest. 1977 Jun;59(6):1196–1202. doi: 10.1172/JCI108744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goldstein J. L., Basu S. K., Brunschede G. Y., Brown M. S. Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans. Cell. 1976 Jan;7(1):85–95. doi: 10.1016/0092-8674(76)90258-0. [DOI] [PubMed] [Google Scholar]
  6. Goldstein J. L., Brown M. S. The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem. 1977;46:897–930. doi: 10.1146/annurev.bi.46.070177.004341. [DOI] [PubMed] [Google Scholar]
  7. Gospodarowicz D., Moran J. S., Braun D. L. Control of proliferation of bovine vascular endothelial cells. J Cell Physiol. 1977 Jun;91(3):377–385. doi: 10.1002/jcp.1040910307. [DOI] [PubMed] [Google Scholar]
  8. Gospodarowicz D., Moran J., Braun D., Birdwell C. Clonal growth of bovine vascular endothelial cells: fibroblast growth factor as a survival agent. Proc Natl Acad Sci U S A. 1976 Nov;73(11):4120–4124. doi: 10.1073/pnas.73.11.4120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kahn C. R. Membrane receptors for hormones and neurotransmitters. J Cell Biol. 1976 Aug;70(2 Pt 1):261–286. doi: 10.1083/jcb.70.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. Nicolson G. L., Lacorbiere M., Hunter T. R. Mechanism of cell entry and toxicity of an affinity- purified lectin from Ricinus communis and its differential effects on normal and virus-transformed fibroblasts. Cancer Res. 1975 Jan;35(1):144–155. [PubMed] [Google Scholar]
  13. Oliver J. M., Ukena T. E., Berlin R. D. Effects of phagocytosis and colchicine on the distribution of lectin-binding sites on cell surfaces. Proc Natl Acad Sci U S A. 1974 Feb;71(2):394–398. doi: 10.1073/pnas.71.2.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Raff M. C., De Petris S. Movement of lymphocyte surface antigens and receptors: the fluid nature of the lymphocyte plasma membrane and its immunological significance. Fed Proc. 1973 Jan;32(1):48–54. [PubMed] [Google Scholar]
  15. Reichl D., Simons L. A., Myant N. B., Pflug J. J., Mills G. L. The lipids and lipoproteins of human peripheral lymph, with observations on the transport of cholesterol from plasma and tissues into lymph. Clin Sci Mol Med. 1973 Sep;45(3):313–329. doi: 10.1042/cs0450313. [DOI] [PubMed] [Google Scholar]
  16. Stein O., Stein Y. High density lipoproteins reduce the uptake of low density lipoproteins by human endothelial cells in culture. Biochim Biophys Acta. 1976 May 27;431(2):363–368. doi: 10.1016/0005-2760(76)90157-0. [DOI] [PubMed] [Google Scholar]
  17. Stein O., Stein Y. Surface binding and interiorization of homologous and heterologous serum lipoproteins by rat aortic smooth muscle cells in culture. Biochim Biophys Acta. 1975 Sep 19;398(3):377–384. doi: 10.1016/0005-2760(75)90188-5. [DOI] [PubMed] [Google Scholar]
  18. Storrie B., Edelson P. J. Distribution of concanavalin A in fibroblasts: direct endocytosis versus surface capping. Cell. 1977 Jul;11(3):707–717. doi: 10.1016/0092-8674(77)90087-3. [DOI] [PubMed] [Google Scholar]
  19. Vasiliev J. M., Gelfand I. M., Domnina L. V., Zacharova O. S., Ljubimov A. V. Contact inhibition of phagocytosis in epithelial sheets: alterations of cell surface properties induced by cell-cell contacts. Proc Natl Acad Sci U S A. 1975 Feb;72(2):719–722. doi: 10.1073/pnas.72.2.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Weinstein D. B., Carew T. E., Steinberg D. Uptake and degradation of low density lipoprotein by swine arterial smoot muscle cells with inhibition of cholesterol biosynthesis. Biochim Biophys Acta. 1976 Mar 26;424(3):404–421. doi: 10.1016/0005-2760(76)90030-8. [DOI] [PubMed] [Google Scholar]
  21. Wright H. P. Mitosis patterns in aortic endothelium. Atherosclerosis. 1972 Jan-Feb;15(1):93–100. doi: 10.1016/0021-9150(72)90042-1. [DOI] [PubMed] [Google Scholar]

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