Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Feb;87(4):1436–1440. doi: 10.1073/pnas.87.4.1436

Focal accumulation of an apolipoprotein B-based synthetic oligopeptide in the healing rabbit arterial wall.

I L Shih 1, R S Lees 1, M Y Chang 1, A M Lees 1
PMCID: PMC53490  PMID: 2304909

Abstract

The functions of surface-accessible domains of apolipoprotein (apo) B, the protein moiety of low density lipoprotein (LDL), are unknown, aside from the LDL receptor-binding domain, which lies toward the carboxyl-terminal end of apoB. Since LDL accumulation in arterial lesions does not depend on recognition of LDLs by a cell-surface receptor, we synthesized an oligopeptide with the sequence of the trypsin-accessible domain of apoB that lies closest to the amino-terminal end of the protein and compared its biological activity to that of another synthetic oligopeptide with the sequence of the heparin- and apoB/apoE receptor-binding domains of apoE. (Tyrosine was added at the amino-terminal end of each peptide to facilitate radiolabeling.) The 18-amino acid apoB-based peptide included residues 1000-1016 of apoB, for which no function has been previously described. In radioautographs, the 125I-labeled peptide accumulated focally at the healing edges of regenerating endothelial islands in the balloon-catheter deendothelialized rabbit aorta. In contrast, the 21-residue apoE-based peptide, which included residues 129-148 of apoE, accumulated diffusely and uniformly throughout the deendothelialized areas of the aorta. The data show that focal binding of the apoB-based peptide can delineate arterial lesions and suggest that this arterial wall-binding domain of apoB mediates accumulation of LDLs in arterial lesions.

Full text

PDF
1436

Images in this article

Selected References

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

  1. BAUMGARTNER H. R. EINE NEUE METHODE ZUR ERZEUGUNG VON THROMBEN DURCH GEZIELTE UBERDEHNUNG DER GEFAESSWAND. Z Gesamte Exp Med. 1963 Sep 12;137:227–247. [PubMed] [Google Scholar]
  2. Bratzler R. L., Chisolm G. M., Colton C. K., Smith K. A., Lees R. S. The distribution of labeled low-density lipoproteins across the rabbit thoracic aorta in vivo. Atherosclerosis. 1977 Nov;28(3):289–307. doi: 10.1016/0021-9150(77)90177-0. [DOI] [PubMed] [Google Scholar]
  3. Camejo G., Olofsson S. O., Lopez F., Carlsson P., Bondjers G. Identification of Apo B-100 segments mediating the interaction of low density lipoproteins with arterial proteoglycans. Arteriosclerosis. 1988 Jul-Aug;8(4):368–377. doi: 10.1161/01.atv.8.4.368. [DOI] [PubMed] [Google Scholar]
  4. Cladaras C., Hadzopoulou-Cladaras M., Nolte R. T., Atkinson D., Zannis V. I. The complete sequence and structural analysis of human apolipoprotein B-100: relationship between apoB-100 and apoB-48 forms. EMBO J. 1986 Dec 20;5(13):3495–3507. doi: 10.1002/j.1460-2075.1986.tb04675.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fischman A. J., Lees A. M., Lees R. S., Barlai-Kovach M., Strauss H. W. Accumulation of native and methylated low density lipoproteins by healing rabbit arterial wall. Arteriosclerosis. 1987 Jul-Aug;7(4):361–366. doi: 10.1161/01.atv.7.4.361. [DOI] [PubMed] [Google Scholar]
  6. Forgez P., Gregory H., Young J. A., Knott T., Scott J., Chapman M. J. Identification of surface-exposed segments of apolipoprotein B-100 in the LDL particle. Biochem Biophys Res Commun. 1986 Oct 15;140(1):250–257. doi: 10.1016/0006-291x(86)91083-1. [DOI] [PubMed] [Google Scholar]
  7. Ginsburg G. S., Walsh M. T., Small D. M., Atkinson D. Reassembled plasma low density lipoproteins. Phospholipid-cholesterol ester-apoprotein B complexes. J Biol Chem. 1984 May 25;259(10):6667–6673. [PubMed] [Google Scholar]
  8. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  9. Hospattankar A. V., Law S. W., Lackner K., Brewer H. B., Jr Identification of low density lipoprotein receptor binding domains of human apolipoprotein B-100: a proposed consensus LDL receptor binding sequence of apoB-100. Biochem Biophys Res Commun. 1986 Sep 30;139(3):1078–1085. doi: 10.1016/s0006-291x(86)80287-x. [DOI] [PubMed] [Google Scholar]
  10. Innerarity T. L., Weisgraber K. H., Arnold K. S., Rall S. C., Jr, Mahley R. W. Normalization of receptor binding of apolipoprotein E2. Evidence for modulation of the binding site conformation. J Biol Chem. 1984 Jun 10;259(11):7261–7267. [PubMed] [Google Scholar]
  11. Isaacsohn J. L., Lees A. M., Lees R. S., Strauss H. W., Barlai-Kovach M., Moore T. J. Adrenal imaging with technetium-99m-labelled low density lipoproteins. Metabolism. 1986 Apr;35(4):364–366. doi: 10.1016/0026-0495(86)90156-3. [DOI] [PubMed] [Google Scholar]
  12. Iverius P. H. The interaction between human plasma lipoproteins and connective tissue glycosaminoglycans. J Biol Chem. 1972 Apr 25;247(8):2607–2613. [PubMed] [Google Scholar]
  13. Kaiser E., Colescott R. L., Bossinger C. D., Cook P. I. Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal Biochem. 1970 Apr;34(2):595–598. doi: 10.1016/0003-2697(70)90146-6. [DOI] [PubMed] [Google Scholar]
  14. Knott T. J., Pease R. J., Powell L. M., Wallis S. C., Rall S. C., Jr, Innerarity T. L., Blackhart B., Taylor W. H., Marcel Y., Milne R. Complete protein sequence and identification of structural domains of human apolipoprotein B. Nature. 1986 Oct 23;323(6090):734–738. doi: 10.1038/323734a0. [DOI] [PubMed] [Google Scholar]
  15. Law S. W., Grant S. M., Higuchi K., Hospattankar A., Lackner K., Lee N., Brewer H. B., Jr Human liver apolipoprotein B-100 cDNA: complete nucleic acid and derived amino acid sequence. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8142–8146. doi: 10.1073/pnas.83.21.8142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lees A. M., Lees R. S., Schoen F. J., Isaacsohn J. L., Fischman A. J., McKusick K. A., Strauss H. W. Imaging human atherosclerosis with 99mTc-labeled low density lipoproteins. Arteriosclerosis. 1988 Sep-Oct;8(5):461–470. doi: 10.1161/01.atv.8.5.461. [DOI] [PubMed] [Google Scholar]
  17. Lees R. S., Garabedian H. D., Lees A. M., Schumacher D. J., Miller A., Isaacsohn J. L., Derksen A., Strauss H. W. Technetium-99m low density lipoproteins: preparation and biodistribution. J Nucl Med. 1985 Sep;26(9):1056–1062. [PubMed] [Google Scholar]
  18. Lees R. S., Lees A. M., Strauss H. W. External imaging of human atherosclerosis. J Nucl Med. 1983 Feb;24(2):154–156. [PubMed] [Google Scholar]
  19. Mahley R. W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988 Apr 29;240(4852):622–630. doi: 10.1126/science.3283935. [DOI] [PubMed] [Google Scholar]
  20. Mahley R. W., Innerarity T. L. Lipoprotein receptors and cholesterol homeostasis. Biochim Biophys Acta. 1983 May 24;737(2):197–222. doi: 10.1016/0304-4157(83)90001-1. [DOI] [PubMed] [Google Scholar]
  21. Roberts A. B., Lees A. M., Lees R. S., Strauss H. W., Fallon J. T., Taveras J., Kopiwoda S. Selective accumulation of low density lipoproteins in damaged arterial wall. J Lipid Res. 1983 Sep;24(9):1160–1167. [PubMed] [Google Scholar]
  22. Stemerman M. B., Spaet T. H., Pitlick F., Cintron J., Lejnieks I., Tiell M. L. Intimal healing. The pattern of reendothelialization and intimal thickening. Am J Pathol. 1977 Apr;87(1):125–142. [PMC free article] [PubMed] [Google Scholar]
  23. Weisgraber K. H., Rall S. C., Jr Human apolipoprotein B-100 heparin-binding sites. J Biol Chem. 1987 Aug 15;262(23):11097–11103. [PubMed] [Google Scholar]
  24. Weisgraber K. H., Rall S. C., Jr, Mahley R. W., Milne R. W., Marcel Y. L., Sparrow J. T. Human apolipoprotein E. Determination of the heparin binding sites of apolipoprotein E3. J Biol Chem. 1986 Feb 15;261(5):2068–2076. [PubMed] [Google Scholar]
  25. Yamamoto T., Davis C. G., Brown M. S., Schneider W. J., Casey M. L., Goldstein J. L., Russell D. W. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 1984 Nov;39(1):27–38. doi: 10.1016/0092-8674(84)90188-0. [DOI] [PubMed] [Google Scholar]
  26. Yang C. Y., Chen S. H., Gianturco S. H., Bradley W. A., Sparrow J. T., Tanimura M., Li W. H., Sparrow D. A., DeLoof H., Rosseneu M. Sequence, structure, receptor-binding domains and internal repeats of human apolipoprotein B-100. Nature. 1986 Oct 23;323(6090):738–742. doi: 10.1038/323738a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES