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Cholesteryl ester accumulation in macrophages resulting from receptor-mediated uptake and degradation of hypercholesterolemic canine beta-very low density lipoproteins.
Open accessAbstract
The synthesis and accumulation of cholesteryl esters by monolayers of mouse peritoneal macrophages was stimulated 20- to 160-fold by incubation with beta-migrating very low density lipoproteins (beta-VLDL, density less than 1.006 g/ml) isolated from the plasma of cholesterol-fed dogs. Three other cholesterol-rich lipoprotein fractions obtained from the plasma of the same hypercholesterolemic dogs, including low density lipoprotein (LDL), cholesterol-induced high density lipoprotein (HDLc), and apo-E HDLc, had little to no stimulatory effect. Plasma VLDL (density less than 1.006 g/ml) from normal dogs did not increase cholesteryl ester formation in macrophages. The enhancement in cholesteryl ester synthesis and accumulation by hypercholesterolemic canine beta-VLDL was due to the presence of a high affinity binding site on the macrophage cell surface that mediated the uptake and lysosomal degradation of the beta-VLDL. Competition studies with fucoidin and dextran sulfate indicated that the receptor for canine beta-VLDL was different from that previously described for human acetylated low density lipoprotein (acetyl-LDL). Prior incubation of macrophage monolayers with either unlabeled canine beta-VLDL or human acetyl-LDL, both of which raised the cellular content of cholesteryl esters, reduced the ability of the cells to degrade 125I-labeled beta-VLDL, suggesting that the receptor for beta-VLDL is subject to regulation. The current findings indicate: 1) that macrophages possess a high affinity receptor that recognizes one of the four cholesterol-rich lipoproteins present in the plasma of cholesterol-fed dogs, beta-VLDL, and 2) that the receptor-mediated ingestion of beta-VLDL leads to cholesteryl ester deposition in these cells.
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Brown, M. S., Ho, Y. K., & Goldstein, J. L. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)70568-7 · Cited by 722
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Pitas, R. E., Boyles, J. K., Lee, S. H., Foss, D., & Mahley, R. W. (1987) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(87)90295-5 · Cited by 693
Self-citation[1] Introduction to the plasma lipoproteins
Gotto, A. M., Pownall, H. J., & Havel, R. J. (1986) · Methods in Enzymology · doi:10.1016/0076-6879(86)28061-1 · Cited by 421
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Zannis, V. I., Kardassis, D., & Zanni, E. E. (1993) · Advances in Human Genetics 21 · doi:10.1007/978-1-4615-3010-7_3 · Cited by 78
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Metadata
- Authors
- Goldstein, J. L., Ho, Y. K., Brown, M. S., Innerarity, T. L., & Mahley, R. W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1980-03
- Volume
- 255
- Issue
- 5
- Pages
- 1839-1848
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1562774482
- Cited by
- 376
- References
- 0
- FWCI
- 49.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
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