Subscribe to RSS
DOI: 10.1055/s-0038-1648401
Aprotinin Does Not Inhibit the Release of PGI2 or vWF from Cultured Human Endothelial Cells
Publication History
Received 12 February 1991
Accepted after revision 24 July 1991
Publication Date:
02 July 2018 (online)
Summary
The release of prostacyclin (PGI2) and von Willebrand factor (vWF) from human umbilical vein endothelial cells (HUVEC) was examined to determine if aprotinin had any effects on these endothelial cell reactions. These end-points were chosen to indicate if this serine protease inhibitor caused alterations in the control of haemostatic function by endothelium, in the light of the improvement in haemostasis seen in patients given aprotinin therapy at the time of open heart surgery. Stimuli used to promote secretion of prostacyclin and vWF were human α-thrombin, histamine, protamine sulphate, poly-L-lysine and phor-bol myristate acetate. Aprotinin (30 pM) had no significant effect on the basal or stimulated release of PGI2 or vWF from HUVEC.
-
References
- 1 Royston D, Bidstrup BP, Taylor KM, Sapsford RN. Effect of aprotinin on the need for blood transfusion after repeat open heart surgery. Lancet 1987; ii: 1289-1291
- 2 Bidstrup BP, Royston D, Taylor KM, Sapsford RN. Reduction in blood loss and blood use after cardiopulmonary bypass with high dose aprotinin (Trasylol). J Thorac Cardiovasc Surg 1989; 97: 364-372
- 3 van Oeveren W, Jansen NJ, Bidstrup BP, Royston D, Westaby S, Neuhof H, Wildevuur CR. Effects of aprotinin on haemostatic mechanisms during cardiopulmonary bypass. Ann Thorac Surg 1987; 44: 640-645
- 4 Freidrich G, Weber C, Bernard C, Hettwer A, Schlosser V. Reduction of blood transfusion requirement in open heart surgery by administration of high dose aprotinin - preliminary results. Thorac Cardiovasc Surgeon 1989; 37: 89-91
- 5 Nievelstein PFEM, de Groot PG. Interaction of blood platelets with the vessel wall. Haemostasis 1988; 18: 342-359
- 6 Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical vein. Identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2743-2756
- 7 Morgan DML. Oxidised poly amines and the growth of human vascular endothelial cells. Prevention of cytotoxic effects by selective acetylation. Biochem J 1987; 242: 347-352
- 8 Harper JF. Peritz’ F test: BASIC program of a robust multiple comparison test for statistical analysis of all differences among group means. Comput Biol Med 1984; 142: 437-445
- 9 Coade SB, van Haaren E, Loizou S, Walport MJ, Denham AM, Pearson JD. Endothelial prostacyclin release in systemic lupus erythematosus. Thromb Haemostas 1989; 61: 97-100
- 10 Ager A, Gordon JL, Moncada S, Pearson JD, Salmon JA, Trevethick MA. Effects of isolation and culture on prostaglandin synthesis by porcine aortic endothelial and smooth muscle cells. J Cell Physiol 1987; 110: 9-16
- 11 Pottinger BE, Paleolog EM, Pearson JD. Von Willebrand factor is an acute phase reactant in man. Thromb Res 1989; 53: 387-394
- 12 Petty RG, Pearson JD. Endothelium - the axis of vascular health and disease. J R Coll Phys (Lond) 1989; 23: 92-102
- 13 Ruggeri ZM, Mannucci PM, Lombardi R, Federici AB, Zimmerman TS. Multimeric composition of factor VIII/von Willebrand factor following administration of DDAVP: implications for pathophysiology and therapy of von Willebrand’s disease subtypes. Blood 1982; 59: 1272-1278
- 14 Salzman EW, Weinstein MJ, Weintraub RM, Ware JA, Thurer RL, Robertson L, Donovan A, Gaffney T, Bertele V, Troll J, Smith M, Chute LE. Treatment with desmopressin acetate to reduce blood loss after cardiac surgery. N Engl J Med 1986; 314: 1402-1406
- 15 Fish KJ, Sarnquist FH, van Steennis C, Mitchell RS, Hilberman M, Jamieson SW, Linet OI, Miller DC. A prospective, randomized study of the effects of prostacyclin on platelets and blood loss during coronary bypass operations. J Thorac Cardiovasc Surg 1986; 91: 436-442
- 16 Dietrich W, Spannagl M, Jochum M, Wendt P, Scramm W, Barankay A, Sebening F, Richter JA. Influence of high dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization. Anesthesiology 1990; 73: 1119-1126
- 17 Marath A, Man W, Taylor KM. Histamine release in paediatric cardiopulmonary bypass - a possible role in the capillary leak syndrome. Agents Actions 1987; 20: 299-302
- 18 Weksler BB, Ley CW, Jaffe EA. Stimulation of endothelial cell prostacyclin production by thrombin, trypsin and the ionophore A23187. J Clin Invest 1978; 62: 923-930
- 19 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: 600-608
- 20 Loesberg C, Gonsalves MD, Zandbergen J, Willems C, van Aken WG. The effect of calcium on the secretion of factor VUI-related antigen by cultured human endothelial cells. Biochim Biophys Acta 1983; 763: 160-168
- 21 Needham L, Hellewell PG, Williams TJ, Gordon JL. Endothelial functional responses and increased vascular permeability induced by polycations. Lab Invest 1988; 59: 538-548
- 22 Birnbaumer L, Brown AM. G proteins and the mechanism of action of hormones, neurotransmitters and autocrine and paracrine regulatory function. Am Rev Respir Dis 1990; 141: S106-14
- 23 Wilks JW, Hui OJ. Aprotinin antagonizes the binding of human chorionic gonadotrophin to its receptor. Endocrinology 1987; 120: 846-952
- 24 Pelikan P, Gimbrone MA, Cotran RS. Distribution and movement of anionic surface sites in cultured human vascular endothelial cells. Atherosclerosis 1979; 32: 69-75
- 25 Mizuta K, Hashimoto E, Yamamura H. Proteolytic activation of protein kinase C by membrane-bound protease in rat liver plasma membrane. Biochem Biophys Res Comm 1985; 131: 1262-1268
- 26 Giddings JL. Von Willebrand factor-physiology. In: Vascular Endothelium in Hemostasis and Thrombosis. Gimbrone Jr MA. (ed) Churchill Livingstone; Edinburgh: 1986. pp 142-168
- 27 Hamilton KK, Fretto LJ, Grierson DS, McKee PA. Effects of plasmin on von Willebrand Factor multimers. J Clin Invest 1985; 76: 261-270
- 28 Thompson AE, Howard MA. Proteolytic cleavage of human von Willebrand Factor induced by enzyme(s) released from polymorphonuclear cells. Blood 1986; 67: 1281-1285
- 29 Radomski MW, Palmer RMJ, Moncada S. The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun 1987; 148: 1482-1489
- 30 Sneddon JM, Vane JR. Endothelium-derived relaxing factor reduces platelet adhesion to bovine endothelial cells. Proc Natl Acad Sci 1988; 85: 2800-2804