Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1978 Oct;62(4):836–846. doi: 10.1172/JCI109196

Interaction of collagen with the lipids of tendon xanthomata.

A R Tall, D M Small, R S Lees
PMCID: PMC371836  PMID: 701482

Abstract

To determine the physical state of lipids in tendon xanthomata, six specimens surgically removed from three patients with familial hypercholesterolemia were studied by microscopy, calorimetry, and x-ray diffraction. The major constituents of the xanthomata were lipid (33% of dry weight) and collagen (24% of dry weight). The principal lipids were cholesterol ester and cholesterol. Light microscopy and thin-section electron microscopy showed occasional clusters of foam cells separated by masses of extracellular collagen. Polarized light microscopy of fresh, minced tissue showed rare droplets of free cholesterol ester. When heated, the tissue shrank abruptly at approximately equal to 70 degrees C and, consequently, a large amount of cholesterol ester was released. Scanning calorimetry of fresh pieces of xanthoma showed a single, broad, reversible liquid crystalline transition of cholesterol ester with peak temperature from 32 to 38 degrees C. The enthalpy (0971 +/- 0.07 cal/g) was reduced compared with the isolated cholesterol ester from each xanthoma (1.1+/-0.01 cal/g). There was a large irreversible collagen denaturation endotherm (peak temperature = 67 degrees C; enthalpy 9.9 cal/g collagen) that corresponded to the tissue shrinkage noted by microscopy. After the collagen denaturation, the sample displayed double-peaked reversible liquid crystalline transitions of cholesterol ester, of enthalpy 1.18 +/- 0.1 cal/g, that were identical to transitions of isolated cholesterol ester. Fibers dissected fron xanthomata were examined by X-ray diffraction at temperatures below and above the cholesterol ester transition. At 20 degrees C there was a weakly oriented equatorial reflection of Bragg spacing 36A, which corresponded to the smectic phase of cholesterol ester, and a series of oriented collagen reflections. At 42 degrees C the cholesterol ester reflection disappeared. Stretched fibers examined at 10 degrees C showed good orientation of collagen and cholesterol ester reflections, and in addition, meridional spacings which indicated oriented crystallization of cholesterol ester. These studies suggest that a major component of tendon xanthomata is extracellular cholesterol ester which displays altered melting and molecular orientation as a result of an interaction with collagen. At xanthoma temperatures, the cholesterol ester is in a smectic liquid crystalline state, probably layered between collagen fibrils, with the long axis of the cholesterolester molecules perpendicular to the axis of the collagen fiber. Such collagen-cholesterol ester interactions may favor the extracellular deposition of cholesterol ester derived either from intracellular sources or directly from plasma lipoproteins.

Full text

PDF
836

Images in this article

840Image
on p.840
843Image
on p.843

Selected References

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

  1. Baes H., van Gent C. M., Pries C. Lipid composition of various types of xanthoma. J Invest Dermatol. 1968 Oct;51(4):286–293. [PubMed] [Google Scholar]
  2. Bhattacharyya A. K., Connor W. E., Mausolf F. A., Flatt A. D. Turnover of xanthoma cholesterol in hyperlipoproteinemia patients. J Lab Clin Med. 1976 Mar;87(3):503–518. [PubMed] [Google Scholar]
  3. Bornstein P. The biosynthesis of collagen. Annu Rev Biochem. 1974;43(0):567–603. doi: 10.1146/annurev.bi.43.070174.003031. [DOI] [PubMed] [Google Scholar]
  4. Deckelbaum R. J., Shipley G. G., Small D. M. Structure and interactions of lipids in human plasma low density lipoproteins. J Biol Chem. 1977 Jan 25;252(2):744–754. [PubMed] [Google Scholar]
  5. Downing D. T. Photodensitometry in the thin-layer chromatographic analysis of neutral lipids. J Chromatogr. 1968 Nov 5;38(1):91–99. doi: 10.1016/0021-9673(68)85011-3. [DOI] [PubMed] [Google Scholar]
  6. Engelman D. M., Hillman G. M. Molecular organization of the cholesteryl ester droplets in the fatty streaks of human aorta. J Clin Invest. 1976 Oct;58(4):997–1007. doi: 10.1172/JCI108554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FLETCHER R. F., GLOSTER J. THE LIPIDS IN XANTHOMATA. J Clin Invest. 1964 Nov;43:2104–2111. doi: 10.1172/JCI105084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  9. Katz S. S., Shipley G. G., Small D. M. Physical chemistry of the lipids of human atherosclerotic lesions. Demonstration of a lesion intermediate between fatty streaks and advanced plaques. J Clin Invest. 1976 Jul;58(1):200–211. doi: 10.1172/JCI108450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Katz S. S., Small D. M., Brook J. G., Lees R. S. The storage lipids in Tangier disease. A physical chemical study. J Clin Invest. 1977 Jun;59(6):1045–1054. doi: 10.1172/JCI108727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lang P. D., Insull W., Jr Lipid droplets in atherosclerotic fatty streaks of human aorta. J Clin Invest. 1970 Aug;49(8):1479–1488. doi: 10.1172/JCI106365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McClain P. E., Wiley E. R. Differential scanning calorimeter studies of the thermal transitions of collagen. Implications on structure and stability. J Biol Chem. 1972 Feb 10;247(3):692–697. [PubMed] [Google Scholar]
  13. Samuel P., Perl W., Holtzman C. M., Rochman N. D., Lieberman S. Long-term kinetics of serum and xanthoma cholesterol radioactivity in patients with hypercholesterolemia. J Clin Invest. 1972 Feb;51(2):266–278. doi: 10.1172/JCI106811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Smith E. B., Slater R. S. The microdissection of large atherosclerotic plaques to give morphologically and topographically defined fractions for analysis. 1. The lipids in the isolated fractions. Atherosclerosis. 1972 Jan-Feb;15(1):37–56. doi: 10.1016/0021-9150(72)90036-6. [DOI] [PubMed] [Google Scholar]
  15. Tall A. R., Atkinson D., Small D. M., Mahley R. W. Characterization of the lipoproteins of atherosclerotic swine. J Biol Chem. 1977 Oct 25;252(20):7288–7293. [PubMed] [Google Scholar]
  16. Tall A. R., Deckelbaum R. J., Small D. M., Shipley G. G. Thermal behavior of human plasma high density lipoprotein. Biochim Biophys Acta. 1977 Apr 26;487(1):145–133. doi: 10.1016/0005-2760(77)90051-0. [DOI] [PubMed] [Google Scholar]
  17. Tall A. R., Small D. M., Deckelbaum R. J., Shipley G. G. Structure and thermodynamic properties of high density lipoprotein recombinants. J Biol Chem. 1977 Jul 10;252(13):4701–4711. [PubMed] [Google Scholar]
  18. Traub W., Piez K. A. The chemistry and structure of collagen. Adv Protein Chem. 1971;25:243–352. doi: 10.1016/s0065-3233(08)60281-8. [DOI] [PubMed] [Google Scholar]
  19. VENABLE J. H., COGGESHALL R. A SIMPLIFIED LEAD CITRATE STAIN FOR USE IN ELECTRON MICROSCOPY. J Cell Biol. 1965 May;25:407–408. doi: 10.1083/jcb.25.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES