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. 1992 Nov;34(5):427–430.

Reduction of plasma cholesterol by lovastatin normalizes erythrocyte membrane fluidity in patients with severe hypercholesterolaemia.

Y Levy 1, R Leibowitz 1, M Aviram 1, J G Brook 1, U Cogan 1
PMCID: PMC1381472  PMID: 1467138

Abstract

The effect of lovastatin on erythrocyte membrane composition and fluidity was investigated in eight patients with severe hypercholesterolaemia (mean LDL-cholesterol of 7.2 mmol l-1). Lovastatin was administered at a dosage of 40-80 mg for 20 weeks and was discontinued for 5 weeks thereafter. Parallel to a 47% fall in plasma LDL cholesterol, there was a significant reduction (P < 0.01) in erythrocyte membrane cholesterol:phospholipid molar ratio, while erythrocyte membrane fluidity assessed by diphenylhexatriene (DPH) fluorescence polarization increased significantly (P < 0.01). Discontinuation of lovastatin resulted in the reversal of erythrocyte membrane composition and fluidity to pre-treatment values.

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Selected References

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  1. Beigel Y., Fuchs J., Snir M., Lurie Y., Green P., Djaldetti M. Lovastatin therapy in heterozygous familial hypercholesterolaemic patients: effect on blood rheology and fibrinogen levels. J Intern Med. 1991 Jul;230(1):23–27. doi: 10.1111/j.1365-2796.1991.tb00402.x. [DOI] [PubMed] [Google Scholar]
  2. CHIAMORI N., HENRY R. J. Study of the ferric chloride method for determination of total cholesterol and cholesterol esters. Am J Clin Pathol. 1959 Apr;31(4):305–309. doi: 10.1093/ajcp/31.4.305. [DOI] [PubMed] [Google Scholar]
  3. Chabanel A., Flamm M., Sung K. L., Lee M. M., Schachter D., Chien S. Influence of cholesterol content on red cell membrane viscoelasticity and fluidity. Biophys J. 1983 Nov;44(2):171–176. doi: 10.1016/S0006-3495(83)84288-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cogan U., Shinitzky M., Weber G., Nishida T. Microviscosity and order in the hydrocarbon region of phospholipid and phospholipid-cholesterol dispersions determined with fluorescent probes. Biochemistry. 1973 Jan 30;12(3):521–528. doi: 10.1021/bi00727a026. [DOI] [PubMed] [Google Scholar]
  5. Cooper R. A. Abnormalities of cell-membrane fluidity in the pathogenesis of disease. N Engl J Med. 1977 Aug 18;297(7):371–377. doi: 10.1056/NEJM197708182970707. [DOI] [PubMed] [Google Scholar]
  6. Cooper R. A., Arner E. C., Wiley J. S., Shattil S. J. Modification of red cell membrane structure by cholesterol-rich lipid dispersions. A model for the primary spur cell defect. J Clin Invest. 1975 Jan;55(1):115–126. doi: 10.1172/JCI107901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cooper R. A., Leslie M. H., Fischkoff S., Shinitzky M., Shattil S. J. Factors influencing the lipid composition and fluidity of red cell membranes in vitro: production of red cells possessing more than two cholesterols per phospholipid. Biochemistry. 1978 Jan 24;17(2):327–331. doi: 10.1021/bi00595a021. [DOI] [PubMed] [Google Scholar]
  8. Cooper R. A., Leslie M. H., Knight D., Detweiler D. K. Red cell cholesterol enrichment and spur cell anemia in dogs fed a cholesterol-enriched atherogenic diet. J Lipid Res. 1980 Nov;21(8):1082–1089. [PubMed] [Google Scholar]
  9. DODGE J. T., MITCHELL C., HANAHAN D. J. The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys. 1963 Jan;100:119–130. doi: 10.1016/0003-9861(63)90042-0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Flamm M., Schachter D. Acanthocytosis and cholesterol enrichment decrease lipid fluidity of only the outer human erythrocyte membrane leaflet. Nature. 1982 Jul 15;298(5871):290–292. doi: 10.1038/298290a0. [DOI] [PubMed] [Google Scholar]
  12. Friedewald W. T., Levy R. I., Fredrickson D. S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972 Jun;18(6):499–502. [PubMed] [Google Scholar]
  13. Grundy S. M. HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med. 1988 Jul 7;319(1):24–33. doi: 10.1056/NEJM198807073190105. [DOI] [PubMed] [Google Scholar]
  14. Koppensteiner R., Minar E., Ehringer H. Effect of lovastatin on hemorheology in type II hyperlipoproteinemia. Atherosclerosis. 1990 Jul;83(1):53–58. doi: 10.1016/0021-9150(90)90130-b. [DOI] [PubMed] [Google Scholar]
  15. Levin G., Cogan U., Levy Y., Mokady S. Riboflavin deficiency and the function and fluidity of rat erythrocyte membranes. J Nutr. 1990 Aug;120(8):857–861. doi: 10.1093/jn/120.8.857. [DOI] [PubMed] [Google Scholar]
  16. MERRILL E. W., GILLILAND E. R., MARGETTS, WG, HATCH F. T. RHEOLOGY OF HUMAN BLOOD AND HYPERLIPEMIA. J Appl Physiol. 1964 May;19:493–496. doi: 10.1152/jappl.1964.19.3.493. [DOI] [PubMed] [Google Scholar]
  17. Quarfordt S. H., Hilderman H. L. Quantitation of the in vitro free cholesterol exchange of human red cells and lipoproteins. J Lipid Res. 1970 Nov;11(6):528–535. [PubMed] [Google Scholar]
  18. Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
  19. Rouser G., Siakotos A. N., Fleischer S. Quantitative analysis of phospholipids by thin-layer chromatography and phosphorus analysis of spots. Lipids. 1966 Jan;1(1):85–86. doi: 10.1007/BF02668129. [DOI] [PubMed] [Google Scholar]
  20. Schick B. P., Schick P. K. The effect of hypercholesterolemia on guinea pig platelets, erythrocytes and megakaryocytes. Biochim Biophys Acta. 1985 Feb 8;833(2):291–302. doi: 10.1016/0005-2760(85)90201-2. [DOI] [PubMed] [Google Scholar]
  21. Schuff-Werner P., Schütz E., Seyde W. C., Eisenhauer T., Janning G., Armstrong V. W., Seidel D. Improved haemorheology associated with a reduction in plasma fibrinogen and LDL in patients being treated by heparin-induced extracorporeal LDL precipitation (HELP). Eur J Clin Invest. 1989 Feb;19(1):30–37. doi: 10.1111/j.1365-2362.1989.tb00192.x. [DOI] [PubMed] [Google Scholar]
  22. Shiga T., Maeda N., Suda T., Kon K., Sekiya M., Oka S. Rheological and kinetic dysfunctions of the cholesterol-loaded, human erythrocytes. Biorheology. 1979;16(4-5):363–369. doi: 10.3233/bir-1979-164-511. [DOI] [PubMed] [Google Scholar]
  23. Shinitzky M., Barenholz Y. Fluidity parameters of lipid regions determined by fluorescence polarization. Biochim Biophys Acta. 1978 Dec 15;515(4):367–394. doi: 10.1016/0304-4157(78)90010-2. [DOI] [PubMed] [Google Scholar]

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