Download PDF
Thromb Haemost 1996; 76(05): 663-669
DOI: 10.1055/s-0038-1650639
Rapid Communication
Schattauer GmbH Stuttgart

Correlation between Oxidized Low Density Lipoproteins and von Willebrand Factor in Chronic Renal Failure

Paul Holvoet
1   The Center for Molecular and Vascular Biology, Belgium
,
Jan Donck
2   The Department of Nephrology, Belgium
,
Michèle Landeloos
1   The Center for Molecular and Vascular Biology, Belgium
,
Els Brouwers
1   The Center for Molecular and Vascular Biology, Belgium
,
Kristel Luijtens
3   The Biostatistical Center for Clinical Trials, University of Leuven, Belgium
,
Jozef Arnout
1   The Center for Molecular and Vascular Biology, Belgium
,
Emmanuel Lesaffre
3   The Biostatistical Center for Clinical Trials, University of Leuven, Belgium
,
Yves Vanrenterghem
2   The Department of Nephrology, Belgium
,
Désiré Collen
1   The Center for Molecular and Vascular Biology, Belgium
› Author Affiliations
Further Information

Publication History

Received 28 June 1996

Accepted after revision 25 July 1996

Publication Date:
11 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

An ELISA specific for a wide spectrum of oxidized apo B-100 in OxLDL was developed and applied to blood samples from 27 control subjects, 20 mild chronic renal failure (MCRF) patients, 21 severe chronic renal failure patients on conservative treatment (SCRF) and 56 severe chronic renal failure patients on maintenance hemodialysis (HEMO). Mean levels of OxLDL were 0.59 mg/dl in controls (95% Cl, 0.52-0.66 mg/dl), and were 2.7-fold (p <0.01), 3.1-fold (p <0.001) and 5.4-fold (p <0.001) higher in MCRF, SCRF and HEMO patients, respectively. Levels of von Willebrand factor, a marker of endothelial injury, were 100 percent in controls (95% Cl, 90-110 percent), and were 1.5-fold (p = NS), 1.6-fold (p <0.01) and 2.1-fold (p <0.001) higher in MCRF, SCRF and HEMO patients, respectively. Multiple regression analysis revealed that the extent of renal failure (F = 14; p = 0.0004) accounted for a significant fraction of the variation in OxLDL levels, also after exclusion of patients with evidence of ischemic atherosclerotic disease (F = 21; p = 0.0001). After adjustment for the extent of renal failure, hemodialysis (F = 5.6; p = 0.021) and LDL cholesterol levels (F = 7.1, p = 0.0095) contributed significantly to the variation in OxLDL levels. Whereas the extent of renal failure contributed only marginally to the individual variations in vWF levels (F = 4.1; p = 0.048), these levels correlated significantly with plasma levels of OxLDL (F=26; p=0.0001). In conclusion, atherogenic OxLDL increase progressively during the development of renal failure suggesting that the oxidation of LDL may be associated with endothelial injury and atherogenesis in these patients.

 

  • References

  • 1 Kannel WB. CHD risk factors. A Framingham study update. Hosp Pract 1990; 25: 119-123
    CrossrefPubMedGoogle Scholar
  • 2 Wissler RW. Update on the pathogenesis of atherosclerosis. Am J Med 1990; 91: 3S-9S
    PubMedGoogle Scholar
  • 3 Ma KW, Greene EL, Raij L. Cardiovascular risk factors in chronic renal failure and hemodialysis populations. Am J Kidney Dis 1992; 19: 505-513
    CrossrefPubMedGoogle Scholar
  • 4 Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974; 290: 697-701
    CrossrefPubMedGoogle Scholar
  • 5 Rostand SG, Kirk KA, Rutsky EA. Relationship of coronary risk factors to hemodialysis -associated ischemic heart disease. Kidney Int 1982; 22: 304-308
    CrossrefPubMedGoogle Scholar
  • 6 Rostand SG, Brunzell JD, Cannon RO, Victor RG. Cardiovascular complications in renal failure. J Am Soc Nephrol 1991 2: 1053-1062
    PubMedGoogle Scholar
  • 7 Attman PO, Samuelsson O, Alaupovic P. Lipoprotein metabolism and renal failure. Am J Kidney Dis 1993; 21: 573-592
    CrossrefPubMedGoogle Scholar
  • 8 Steinberg D, Witztum JL. Lipoproteins and atherogenesis: current concepts. J Am Med Assoc 1990; 264: 3047-3052
    CrossrefPubMedGoogle Scholar
  • 9 Ross R. The pathogenesis of atherosclerosis: an update: a perspective for the 1990‘s. Nature 1993; 362: 801-809
    CrossrefPubMedGoogle Scholar
  • 10 Holvoet P, Collen D. Oxidized lipoproteins in atherosclerosis and thrombosis. FASEB J 1994; 8: 1279-1284
    CrossrefPubMedGoogle Scholar
  • 11 Holvoet P, Perez G, Bernar H, Brouwers E, Vanloo B, Rosseneu M, Collen D. Stimulation with a monoclonal antibody (mAb4E4) of scavenger receptor-mediated uptake of chemically modified low density lipoproteins by THP-1 derived macrophages enhances foam cell generation. J Clin Invest 1994; 93: 89-98
    CrossrefPubMedGoogle Scholar
  • 12 Holvoet P, Perez G, Zhao Z, Brouwers E, Bernar H, Collen D. Malondial-dehyde-modified low density lipoproteins in patients with atherosclerotic disease. J Clin Invest 1995; 95: 2611-2619
    CrossrefPubMedGoogle Scholar
  • 13 Salonen JT, Yla-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssonen K, Palinski W, Witztum JL. Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 1992; 339: 883-887
    CrossrefPubMedGoogle Scholar
  • 14 Maggi E, Bellazzi R, Gazo A, Seccia M, Bellomo G. Autoantibodies against oxidatively-modified LDL in uremic patients undergoing dialysis. Kidney Int 1994; 46: 869-876
    CrossrefPubMedGoogle Scholar
  • 15 Reidy MA, Chopek M, Chao S, McDonal T, Schwartz SM. Injury induces increase of von Willebrand factor in rat endothelial cells. Am J Pathol 1989; 134: 857-864
    PubMedGoogle Scholar
  • 16 Jansson JH, Nilsson TK, Johnson O. von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death. Br Heart J 1991; 66: 351-355
    CrossrefPubMedGoogle Scholar
  • 17 Degoulet P, Legrain M, Reach I, Aime F, Devries C, Rojas P, Jacobs C. Mortality risk factors in patients treated by chronic hemodialysis. Nephron 1982; 31: 103-110
    CrossrefPubMedGoogle Scholar
  • 18 Neff MS, Eiser AR, Slifkin RF, Baum M, Baez A, Gupta S, Amarga E. Patients surviving 10 years of hemodialysis. Am J Med 1983; 74: 996-1004
    CrossrefPubMedGoogle Scholar
  • 19 Havel RJ, Eder HA, Bragdon JH. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human sera. J Clin Invest 1955; 34: 1345-1353
    CrossrefPubMedGoogle Scholar
  • 20 Haberland MD, Fogelman AM, Edwards PA. Specificity of receptor-mediated recognition of malondialdehyde-modified low density lipoproteins. Proc Natl Acad Sci 1982; 79: 1712-1716
    CrossrefPubMedGoogle Scholar
  • 21 Steinbrecher UP. Oxidation of low density lipoprotein results in derivatiza-tion of lysine residues of apolipoprotein B by lipid peroxide decomposition products. J Biol Chem 1987; 262: 3603-3608
    PubMedGoogle Scholar
  • 22 Sparrow CP, Parthasarathy S, Steinberg D. Enzymatic modification of low density lipoprotein by purified lipoxygenase plus phospholipase A2 mimics cell-mediated oxidative modification. J Lipid Res 1988; 29: 745-753
    PubMedGoogle Scholar
  • 23 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41
    CrossrefPubMedGoogle Scholar
  • 24 Reade V, Tailleux A, Reade R, Harduin P, Cachera C, Tacquet A, Fruchart JC, Fievet C. Expression of apolipoprotein B epitopes in low density lipoproteins of hemodialyzed patients. Kidney Int 1993; 44: 1360-1365
    CrossrefPubMedGoogle Scholar
  • 25 Hoff HF, O‘Neil J. Lesion-derived low density lipoprotein and oxidized low density lipoprotein share a lability for aggregation, leading to enhanced macrophage degradation. Arterioscler Thromb 1991; 11: 1209-1222
    CrossrefPubMedGoogle Scholar
  • 26 Steinbrecher UP, Lougheed M. Scavenger-receptor-independent stimulation of cholesterol esterification in macrophages by low density lipoprotein extracted from human aortic intima. Arterioscler Thromb 1992; 12: 608-625
    CrossrefPubMedGoogle Scholar
  • 27 van Berkel TJ, Ziere GJ, Bijsterbosch MK, Kuiper J. Lipoprotein receptors and atherogenic receptor-mediated mechanisms. Curr Opin Lipidol 1994; 5: 331-338
    CrossrefPubMedGoogle Scholar
  • 28 Gonen B, Goldberg AP, Harter RH, Schonfeld G. Abnormal cell-interactive properties of low-density lipoproteins isolated from patients with chronic renal failure. Metabolism 1985; 34: 10-14
    CrossrefPubMedGoogle Scholar
  • 29 Reinhart WH. Shear-dependence of endothelial functions. Experentia 1994; 50: 87-93
    CrossrefPubMedGoogle Scholar
  • 30 Haaber AB, Eidemark I, Jensen T, Feldt-Rasmussen B, Strandgaard S. Vascular endothelial cell function and cardiovascular risk factors in patients with chronic renal failure. J Am Soc Nephrol 1995; 5: 1581-1584
    PubMedGoogle Scholar
  • 31 Keane WF, Mulcahy WS, Kasiske BL, Kim Y, O‘Donnell MP. Hyper-lipidemia and progressive renal disease. Kidney Int 1991; Suppl 39: S41-48
    PubMedGoogle Scholar
  • 32 Trachtman H, Schwob N, Maesaka J, Valderrama E. Dietary supplementation ameliorates renal injury in chronic puromycin aminonucleoside nephropathy. J Am Soc Nephrol 1995; 5: 1811-1819
    PubMedGoogle Scholar
  • 33 Steinberg D. Clinical trials of antioxidants in atherosclerosis: are we doing the right thing?. Lancet 1995; 346: 36-38
    CrossrefPubMedGoogle Scholar
  • 34 Rasmussen O, Thomsen C, Ingerslev J, Hermansen K. Decrease of von Willebrand factor levels after a high-monounsaturated fat diet in noninsulin-dependent diabetic subjects. Metabolism 1994; 43: 1406-1409
    CrossrefPubMedGoogle Scholar
  • 35 Blann AD, Jackson P, Bath PM, Watts GF. von Willebrand factor, a possible indicator of endothelial cell damage, decreases during long-term compliance with a lipid-lowering diet. J Intern Med 1995; 237: 557-561
    CrossrefPubMedGoogle Scholar
  • 36 Reverter JC, Escolar G, Sanz C, Cases A, Villamor N, Nieuwenhuis HK, Lopez J, Ordinas A. Platelet activation during hemodialysis measured through exposure of P-selectin: analysis by flow cytometric and ultrastruc-tural techniques. J Lab Clin Med 1994; 124: 79-85
    PubMedGoogle Scholar
  • 37 Zwaginga JJ, Koomans HA, Sixma JJ, Rabelink TJ. Thrombus formation and platelet-vessel wall interaction in the nephrotic syndrome under flow conditions. J Clin Invest 1994; 93: 204-211
    CrossrefPubMedGoogle Scholar
  • 38 Zhao B, Dierichs R, Harrachruprecht B, Winterhorff H. Oxidized LDL induces serotonin release from blood platelets. Am J Hematol 1995; 48: 285-287
    CrossrefPubMedGoogle Scholar
  • 39 Pocock SJ. Subgroup analysis. In: Clinical trial A practical approach. Pocock SJ. ed. Wiley J & Sons, Chichester; 1993. pp 211-218