von Willebrand Factor (vWf) as a Plasma Marker of Endothelial Activation in Diabetes: Improved Reliability with Parallel Determination of the vWf Propeptide (vWf:AgII)

Ulrich Vischer; Jef J. Emeis; Henk J. G. Bilo; Coen D. A. Stehouwer; Claus Thomsen; Ole Rasmussen; Kjeld Hermansen; Claes B. Wollheim; Jørgen Ingerslev

doi:10.1055/s-0037-1615401

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1998; 80(06): 1002-1007
DOI: 10.1055/s-0037-1615401

Letters to the Editor

Schattauer GmbH

von Willebrand Factor (vWf) as a Plasma Marker of Endothelial Activation in Diabetes: Improved Reliability with Parallel Determination of the vWf Propeptide (vWf:AgII)

Ulrich Vischer

¹Division de Biochimie Clinique, Department of Internal Medicine, HCU, Geneva, Switzerland

,

Jef J. Emeis

²Division of Vascular and Connective Tissue Research, Gaubius Laboratory TNO-PG, Leiden, The Netherlands

,

Henk J. G. Bilo

³Department of Internal Medicine, Weezenlanden Hospital, Zwolle, The Netherlands

,

Coen D. A. Stehouwer

⁴Department of Internal Medicine, Aacademisch Ziekenhuis Vrije Universiteit, Amsterdam, The Netherlands

,

Claus Thomsen

⁵Department of Endocrinology and Metabolism

,

Ole Rasmussen

⁵Department of Endocrinology and Metabolism

,

Kjeld Hermansen

⁵Department of Endocrinology and Metabolism

,

Claes B. Wollheim

¹Division de Biochimie Clinique, Department of Internal Medicine, HCU, Geneva, Switzerland

,

Jørgen Ingerslev

⁶Center for Hemophilia and Thrombosis, Aarhus University Hospital, Aarhus, Denmark

› Institutsangaben

Abstract

Summary

Elevated plasma von Willebrand factor (vWf) levels are found in diabetes and other vasculopathies, and predict cardiovascular mortality. vWf is stored and released from endothelial cell secretory granules, along with equimolar amounts of its propeptide (vWf:AgII). In the present study, we examined plasma propeptide levels as a marker of endothelial secretion in vivo, using an ELISA based on monoclonal antibodies. vWf but not propeptide levels are influenced by blood groups, explaining in part the smaller variation in plasma propeptide levels among normal individuals. In both controls and insulin-dependent diabetic patients, we found a close correlation between propeptide and immunoreactive vWf levels (r² = 0.54, p <0.0001). vWf and propeptide were elevated in patient subgroups with microalbuminuria or overt diabetic nephropathy, whereas only the propeptide was significantly elevated in the normoalbuminuric subgroup. This observation suggests that in conjunction with vWf, propeptide measurements may improve the identification of endothelial activation, which occurs frequently even without increased urinary albumin excretion. In 12 NIDDM patients, a 3-week diet enriched in monounsaturated fat (MUFA) resulted in parallel decreases in vWf (-22%, p <0.05) and propeptide (-17%, p <0.05) levels, indicating that the experimental diet affected endothelial secretion rather than vWf catabolism. A carbohydrate-enriched control diet did not significantly influence either marker.

Our results suggest that concomittant determinations of plasma vWf and propeptide are useful tools to assess endothelial activation in vivo, and reinforce our previous conclusion that a diet rich in MUFA can improve endothelial function in NIDDM.

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References
1 Jensen T, Bjerre-Knudsen J, Feldt-Rasmussen B, Deckert T. Features of endothelial dysfunction in early diabetic nephropathy. Lancet 1989; I: 461-3.
2 Stehouwer CDA, Stroes ESG, Hackeng WHL, Mulder PGH, den Ottolander GJH. von Willebrand Factor and development of diabetic nephropathy in IDDM. Diabetes 1991; 40: 971-6.
3 El Khawand C, Jamart J, Donckier J, Chatelain B, Lavenne E, Moriau M, Buysschaert M. Hemostasis variables in type I diabetic patients without demonstrable vascular complications. Diabetes Care 1993; 16: 1137-45.
4 Knöbl P, Schernthaner G, Schnack C Pietschmann P, Griesmacher A, Prager R, Muller M. Thrombogenic factors are related to urinary albumin excretion rate in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993; 36: 1045-50.
5 Pedrinelli R, Giampietro O, Carmassi F, Melillo E, Dell’Omo G, Catapano G, Matteucci E, Talarico L, Morale M, de Negri F, di Bello V. Micro-albuminuria and endothelial dysfunction in essential hypertension. Lancet 1994; 344: 14-8.
6 Stehouwer CDA, Fischer HRA, van Kuijk AWR, Polak BCP, Donker AJM. Endothelial dysfunction precedes development of microalbuminuria in IDDM. Diabetes 1995; 44: 561-4.
7 Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. for the European Concerted Action on Thrombosis and disabilities angina pectoris study group. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. New Engl J Med 1995; 332: 635-41.
8 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: 351-5.
9 Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69: 1691-5.
10 Matsui T, Fujimura Y, Nishida S, Titani K. Human plasma α₂-macroglobulin and von Willebrand factor possess covalently linked AB0 (H) blood group antigens in subjects with corresponding AB0 phenotype. Blood 1983; 82: 663-8.
11 Wagner DD. Cell biology of von Willebrand factor. Ann Rev Cell Biol 1990; 6: 217-46.
12 Bowie EJW, Solberg LA, Fass DN Johnson DM, Knutson GJ, Stewart ML. et al. Transplantation of normal bone marrow into a pig with severe von Willebrand disease. J Clin Invest 1986; 78: 26-30.
13 Vischer UM, Wagner DD. von Willebrand factor proteolytic processing and multimerization precede the formation of Weibel-Palade bodies. Blood 1994; 83: 3536-44.
14 Wagner DD, Fay PJ, Sporn LA, Sinha S, Lawrence SO, Marder VJ. Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells. Proc Natl Acad Sci 1987; 84: 1955-9.
15 Vischer UM, Ingerslev J, Wollheim CB, Mestries JC, Tsakiris DA, Haefeli WE. et al. Acute von Willebrand factor secretion from the endothelium in vivo: Assessement through plasma propeptide (vWf:AgII) levels. Thromb Haemost 1997; 77: 387-93.
16 Borchiellini A, Fijnvandraat K, ten Cate JW, Pajkrt D, van Deventer SJH Pasterkamp G, Meijer-Huizinga F, Zwart-Huinink L, Voorberg J, van Mourik JA. Quantitative analysis of von Willebrand factor propeptide release in vivo: Effect of experimental endotoxinemia and administration of DDAVP in humans. Blood 1996; 88: 2951-8.
17 McCarroll DR, Ruggeri ZM, Montgomery RR. Correlation between circulating levels of von Willebrand’s antigen II and von Willebrand factor: discrimination between type I and type II von Willebrand’s disease. J lab Clin Med 1984; 103: 704-11.
18 Rasmussen O, Thomsen C, Ingerslev J, Hermansen K. Decrease in von Willebrand factor levels after a high-monounsaturated-fat diet in non-insulin-dependent diabetic subjects. Metabolism 1994; 43: 1406-9.
19 van Kesteren PJM, Kooistra T, Lansink M, van Kamp GJ, Asscheman H, Gooren LJG, Emeis JJ, Vischer UM, Stehouwer CDA. The effect of sex steroids on plasma levels of marker proteins of endothelial cell functioning. Thromb Haemost 1998; 79: 1029-33.
20 Koh KK, Mincemoyer R, Bui MN, Csako G, Pucino F, Guetta V, Waclawiw M, Cannon RO. Effects of hormone replacement therapy on fibrinolysis in postmenopausal women. New Engl J Med 1997; 336: 683-90.
21 Birch KA, Pober JS, Zavoico GB, Means AR, Ewenstein BM. Calcium/ calmodulin transduces thrombin-stimulated secretion: studies in intact and minimally permeabilized human umbilical vein endothalial cells. J Cell Biol 1992; 118: 1501-10.
22 Hamilton KK, Sims PJ. Changes in cytosolic Ca²⁺ associated with von Willebrand factor release in human endothelial cells exposed to histamine. J Clin Invest 1987; 79: 600-8.
23 Mordes DB, Lazarchick J, Colwell JA, Sens DA. Elevated glucose concentrations increase factor VIIIR:Ag levels in human umbilical vein endothelial cells. Diabetes 1983; 32: 876-878.
24 Pinsky DJ, Naka Y, Liao H, Oz MC, Wagner DD, Mayadas TN Hohnson RC, Hynes RO, Heath M, Lawson CA, Stern DM. Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation. J Clin Invest 1996; 97: 493-500.
25 Wautier JL, Wautier MP, Schmidt AM, Anderson GM, Hori O, Zoukourian C Capron L, Chappey O, Yan SD, Brett J, Guillausseau PJ, Stern D. Advanced glycation end products (AGEs) on the surface of diabetic erythrocytes bind to the vessel wall via a specific receptor inducing oxidant stress in the vasculature: a link between surface-associated AGEs and diabetic complications. Proc Natl Acad Sci USA 1994; 91: 7742-6.
26 Vossen RC, van Dam Mieras MC, Hornstra G, Zwaal RF. Differential effects on endothelial cell fatty acid modification on the sensitivity of their membranes phospholopids to peroxidation. Prostaglandins Leukot Essent Fatty Acids. 1995; 52: 431-7.
27 O’Keefe JH, Lavie CJ, McCallister BD. Insights into the pathogenesis and prevention of coronary artery disease. Mayo Clin Proc 1995; 70: 69-79.
28 Vischer UM, Jornot L, Wollheim CB, Theler JM. Reactive oxygen intermediates induce regulated secretion of von Willebrand factor from cultured human vascular endothelial cells. Blood 1995; 85: 3164-72.