Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1993 Jun;142(6):1804–1812.

Renal apolipoproteins in nephrotic rats.

H van Goor 1, M L van der Horst 1, J Atmosoerodjo 1, J A Joles 1, A van Tol 1, J Grond 1
PMCID: PMC1886974  PMID: 8506949

Abstract

Recent experimental data suggest a role for lipids in the pathogenesis of glomerulosclerosis. In this study, we examined the main apolipoproteins (apo) of high density lipoproteins (A-I, A-IV, E), low density lipoproteins (B), and very low density lipoproteins (B,E) in plasma and kidney tissue of rats with puromycin aminonucleoside or adriamycin nephrosis. In full-blown nephrosis, plasma concentrations of apo A-I and apo B were significantly elevated, apo A-IV and apo E levels did not change. Immunohistological studies in plastic sections revealed increased apo A-I, apo A-IV, and apo E immunoreactivity in glomerular visceral epithelial cells both in puromycin aminonucleoside and adriamycin nephrosis. This was confirmed by immunoelectronmicroscopy. In addition, apo B and apo E were encountered in increased amounts in the mesangium and colocalized with Oil Red O-positive lipid deposits, particularly in puromycin aminonucleoside nephrosis rats. Double-staining showed a preferential localization of apo B and apo E at sites of increased mesangial matrix in close proximity to ED1-positive foam cells, i.e., the mesangial macrophages. The close topographic association between apo B and apo E, lipid deposits, and macrophages in the mesangium lend further support to the concept of lipid-mediated glomerular injury in nephrosis.

Full text

PDF

Images in this article

1808Figure 1
on p.1808
1808Figure 2
on p.1808
1808Figure 3
on p.1808
1808Figure 4
on p.1808
1808Figure 5
on p.1808
1808Figure 6
on p.1808
1809Figure 7
on p.1809
1810Figure 8/9
on p.1810

Selected References

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

  1. Al-Shebeb T., Frohlich J., Magil A. B. Glomerular disease in hypercholesterolemic guinea pigs: a pathogenetic study. Kidney Int. 1988 Feb;33(2):498–507. doi: 10.1038/ki.1988.26. [DOI] [PubMed] [Google Scholar]
  2. Appel G. Lipid abnormalities in renal disease. Kidney Int. 1991 Jan;39(1):169–183. doi: 10.1038/ki.1991.22. [DOI] [PubMed] [Google Scholar]
  3. Babaev V. R., Dergunov A. D., Chenchik A. A., Tararak E. M., Yanushevskaya E. V., Trakht I. N., Sorg C., Smirnov V. N. Localization of apolipoprotein E in normal and atherosclerotic human aorta. Atherosclerosis. 1990 Dec;85(2-3):239–247. doi: 10.1016/0021-9150(90)90116-z. [DOI] [PubMed] [Google Scholar]
  4. Bass J., Fisher E. A., Prack M. M., Williams D. L., Marsh J. B. Macrophages from nephrotic rats regulate apolipoprotein E biosynthesis and cholesterol content independently. J Clin Invest. 1991 Feb;87(2):470–475. doi: 10.1172/JCI115019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Basu S. K., Goldstein J. L., Brown M. S. Independent pathways for secretion of cholesterol and apolipoprotein E by macrophages. Science. 1983 Feb 18;219(4586):871–873. doi: 10.1126/science.6823554. [DOI] [PubMed] [Google Scholar]
  6. Bernard D. B. Extrarenal complications of the nephrotic syndrome. Kidney Int. 1988 Jun;33(6):1184–1202. doi: 10.1038/ki.1988.129. [DOI] [PubMed] [Google Scholar]
  7. Bocan T. M., Brown S. A., Guyton J. R. Human aortic fibrolipid lesions. Immunochemical localization of apolipoprotein B and apolipoprotein A. Arteriosclerosis. 1988 Sep-Oct;8(5):499–508. doi: 10.1161/01.atv.8.5.499. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Calandra S., Tarugi P., Ghisellini M., Gherardi E. Plasma and urine lipoproteins during the development of nephrotic syndrome induced in the rat by adriamycin. Exp Mol Pathol. 1983 Dec;39(3):282–299. doi: 10.1016/0014-4800(83)90058-8. [DOI] [PubMed] [Google Scholar]
  10. Cardin A. D., Barnhart R. L., Witt K. R., Jackson R. L. Reactivity of heparin with the human plasma heparin-binding proteins thrombin, antithrombin III, and apolipoproteins E and B-100. Thromb Res. 1984 Jun 15;34(6):541–550. doi: 10.1016/0049-3848(84)90258-5. [DOI] [PubMed] [Google Scholar]
  11. Cardin A. D., Randall C. J., Hirose N., Jackson R. L. Physical-chemical interaction of heparin and human plasma low-density lipoproteins. Biochemistry. 1987 Aug 25;26(17):5513–5518. doi: 10.1021/bi00391a045. [DOI] [PubMed] [Google Scholar]
  12. Dallinga-Thie G. M., Groot P. H., van Tol A. Electroimmunoassay of rat apolipoproteins A-I, A-IV, and E. A procedure for sample treatment to increase the sensitivity in diluted fractions. J Lipid Res. 1985 Jul;26(7):889–892. [PubMed] [Google Scholar]
  13. Dallinga-Thie G. M., Van 't Hooft F. M., Van Tol A. Tissue sites of degradation of high density lipoprotein apolipoprotein A-IV in rats. Arteriosclerosis. 1986 May-Jun;6(3):277–284. doi: 10.1161/01.atv.6.3.277. [DOI] [PubMed] [Google Scholar]
  14. Diamond J. R., Ding G., Frye J., Diamond I. P. Glomerular macrophages and the mesangial proliferative response in the experimental nephrotic syndrome. Am J Pathol. 1992 Oct;141(4):887–894. [PMC free article] [PubMed] [Google Scholar]
  15. Diamond J. R., Hanchak N. A., McCarter M. D., Karnovsky M. J. Cholestyramine resin ameliorates chronic aminonucleoside nephrosis. Am J Clin Nutr. 1990 Apr;51(4):606–611. doi: 10.1093/ajcn/51.4.606. [DOI] [PubMed] [Google Scholar]
  16. Diamond J. R., Karnovsky M. J. Exacerbation of chronic aminonucleoside nephrosis by dietary cholesterol supplementation. Kidney Int. 1987 Nov;32(5):671–677. doi: 10.1038/ki.1987.259. [DOI] [PubMed] [Google Scholar]
  17. Diamond J. R., Karnovsky M. J. Focal and segmental glomerulosclerosis: analogies to atherosclerosis. Kidney Int. 1988 May;33(5):917–924. doi: 10.1038/ki.1988.87. [DOI] [PubMed] [Google Scholar]
  18. Diamond J. R., Pesek-Diamond I. Sublethal X-irradiation during acute puromycin nephrosis prevents late renal injury: role of macrophages. Am J Physiol. 1991 Jun;260(6 Pt 2):F779–F786. doi: 10.1152/ajprenal.1991.260.6.F779. [DOI] [PubMed] [Google Scholar]
  19. Diamond J. R., Pesek I. Glomerular tumor necrosis factor and interleukin 1 during acute aminonucleoside nephrosis. An immunohistochemical study. Lab Invest. 1991 Jan;64(1):21–28. [PubMed] [Google Scholar]
  20. Diamond J. R., Pesek I., McCarter M. D., Karnovsky M. J. Altered functional characteristics of rat macrophages during nephrosis. Synergistic effects of hypercholesterolemia. Am J Pathol. 1989 Oct;135(4):711–718. [PMC free article] [PubMed] [Google Scholar]
  21. Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
  22. French S. W., Yamanaka W., Ostwald R. Dietary induced glomerulosclerosis in the guinea pig. Arch Pathol. 1967 Feb;83(2):204–210. [PubMed] [Google Scholar]
  23. Gherardi E., Calandra S. Plasma and urinary lipids and lipoproteins during the development of nephrotic syndrome induced in the rat by puromycin aminonucleoside. Biochim Biophys Acta. 1982 Feb 15;710(2):188–196. doi: 10.1016/0005-2760(82)90149-7. [DOI] [PubMed] [Google Scholar]
  24. Glass C. K., Pittman R. C., Keller G. A., Steinberg D. Tissue sites of degradation of apoprotein A-I in the rat. J Biol Chem. 1983 Jun 10;258(11):7161–7167. [PubMed] [Google Scholar]
  25. Gordon V., Innerarity T. L., Mahley R. W. Formation of cholesterol- and apoprotein E-enriched high density lipoproteins in vitro. J Biol Chem. 1983 May 25;258(10):6202–6212. [PubMed] [Google Scholar]
  26. Groener J. E., van Gent T., van Tol A. Effect of lipid transfer protein on plasma lipids, apolipoproteins and metabolism of high-density lipoprotein cholesteryl ester in the rat. Biochim Biophys Acta. 1989 Mar 14;1002(1):93–100. doi: 10.1016/0005-2760(89)90070-2. [DOI] [PubMed] [Google Scholar]
  27. Grond J., Muller E. W., Weening J. J. Genetic differences in susceptibility to glomerular sclerosis: a role for lipids? Am J Med. 1989 Nov;87(5N):30N–33N. [PubMed] [Google Scholar]
  28. Grond J., Weening J. J., Elema J. D. Glomerular sclerosis in nephrotic rats. Comparison of the long-term effects of adriamycin and aminonucleoside. Lab Invest. 1984 Sep;51(3):277–285. [PubMed] [Google Scholar]
  29. Grond J., van Goor H., Erkelens D. W., Elema J. D. Glomerular sclerotic lesions in the rat. Histochemical analysis of their macromolecular and cellular composition. Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;51(6):521–534. doi: 10.1007/BF02899057. [DOI] [PubMed] [Google Scholar]
  30. Gröne H. J., Walli A., Gröne E., Niedmann P., Thiery J., Seidel D., Helmchen U. Induction of glomerulosclerosis by dietary lipids. A functional and morphologic study in the rat. Lab Invest. 1989 Mar;60(3):433–446. [PubMed] [Google Scholar]
  31. Kanwar Y. S., Liu Z. Z., Kashihara N., Wallner E. I. Current status of the structural and functional basis of glomerular filtration and proteinuria. Semin Nephrol. 1991 Jul;11(4):390–413. [PubMed] [Google Scholar]
  32. Kasiske B. L., O'Donnell M. P., Cleary M. P., Keane W. F. Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats. Kidney Int. 1988 Mar;33(3):667–672. doi: 10.1038/ki.1988.51. [DOI] [PubMed] [Google Scholar]
  33. Kasiske B. L., O'Donnell M. P., Garvis W. J., Keane W. F. Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure. Circ Res. 1988 Feb;62(2):367–374. doi: 10.1161/01.res.62.2.367. [DOI] [PubMed] [Google Scholar]
  34. Kasiske B. L., O'Donnell M. P., Schmitz P. G., Kim Y., Keane W. F. Renal injury of diet-induced hypercholesterolemia in rats. Kidney Int. 1990 Mar;37(3):880–891. doi: 10.1038/ki.1990.62. [DOI] [PubMed] [Google Scholar]
  35. Keane W. F., Kasiske B. L. Hyperlipidemia in the nephrotic syndrome. N Engl J Med. 1990 Aug 30;323(9):603–604. doi: 10.1056/NEJM199008303230910. [DOI] [PubMed] [Google Scholar]
  36. Keane W. F., Kasiske B. L., O'Donnell M. P. Lipids and progressive glomerulosclerosis. A model analogous to atherosclerosis. Am J Nephrol. 1988;8(4):261–271. doi: 10.1159/000167599. [DOI] [PubMed] [Google Scholar]
  37. Klein D. J., Dehnel P. J., Oegema T. R., Brown D. M. Alterations in proteoglycan metabolism in the nephrotic syndrome induced by the aminonucleoside of puromycin. Lab Invest. 1984 May;50(5):543–551. [PubMed] [Google Scholar]
  38. Marsh J. B., Sparks C. E. Lipoproteins in experimental nephrosis: plasma levels and composition. Metabolism. 1979 Oct;28(10):1040–1045. doi: 10.1016/0026-0495(79)90008-8. [DOI] [PubMed] [Google Scholar]
  39. Moorhead J. F. Lipids and progressive kidney disease. Kidney Int Suppl. 1991 Apr;31:S35–S40. [PubMed] [Google Scholar]
  40. Oschry Y., Eisenberg S. Rat plasma lipoproteins: re-evaluation of a lipoprotein system in an animal devoid of cholesteryl ester transfer activity. J Lipid Res. 1982 Nov;23(8):1099–1106. [PubMed] [Google Scholar]
  41. Rabelink A. J., Hené R. J., Erkelens D. W., Joles J. A., Koomans H. A. Effects of simvastatin and cholestyramine on lipoprotein profile in hyperlipidaemia of nephrotic syndrome. Lancet. 1988 Dec 10;2(8624):1335–1338. doi: 10.1016/s0140-6736(88)90870-7. [DOI] [PubMed] [Google Scholar]
  42. Scanu A. M. Physiopathology of plasma lipoprotein metabolism. Kidney Int Suppl. 1991 Apr;31:S3–S7. [PubMed] [Google Scholar]
  43. Schreiner G. F., Unanue E. R. Origin of the rat mesangial phagocyte and its expression of the leukocyte common antigen. Lab Invest. 1984 Nov;51(5):515–523. [PubMed] [Google Scholar]
  44. Shimano H., Yamada N., Katsuki M., Shimada M., Gotoda T., Harada K., Murase T., Fukazawa C., Takaku F., Yazaki Y. Overexpression of apolipoprotein E in transgenic mice: marked reduction in plasma lipoproteins except high density lipoprotein and resistance against diet-induced hypercholesterolemia. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1750–1754. doi: 10.1073/pnas.89.5.1750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Van Tol A., Jansen E. H., Koomans H. A., Joles J. A. Hyperlipoproteinemia in Nagase analbuminemic rats: effects of pravastatin on plasma (apo)lipoproteins and lecithin:cholesterol acyltransferase activity. J Lipid Res. 1991 Nov;32(11):1719–1728. [PubMed] [Google Scholar]
  46. Van't Hooft F. M., Van Tol A. The sites of degradation of rat high-density-lipoprotein apolipoprotein E specifically labelled with O-(4-diazo-3-[125I]iodobenzoyl)sucrose. Biochem J. 1985 Mar 15;226(3):715–721. doi: 10.1042/bj2260715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yamada N., Inoue I., Kawamura M., Harada K., Watanabe Y., Shimano H., Gotoda T., Shimada M., Kohzaki K., Tsukada T. Apolipoprotein E prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits. J Clin Invest. 1992 Feb;89(2):706–711. doi: 10.1172/JCI115639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. van Goor H., Fidler V., Weening J. J., Grond J. Determinants of focal and segmental glomerulosclerosis in the rat after renal ablation. Evidence for involvement of macrophages and lipids. Lab Invest. 1991 Jun;64(6):754–765. [PubMed] [Google Scholar]
  49. van Goor H., van der Horst M. L., Fidler V., Grond J. Glomerular macrophage modulation affects mesangial expansion in the rat after renal ablation. Lab Invest. 1992 May;66(5):564–571. [PubMed] [Google Scholar]
  50. van't Hooft F. M., van Tol A. The sites of degradation of purified rat low density lipoprotein and high density lipoprotein in the rat. Biochim Biophys Acta. 1985 Oct 2;836(3):344–353. doi: 10.1016/0005-2760(85)90138-9. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES