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DOI: 10.1055/s-0038-1649723
Effects of Homocysteine and Related Compounds on Prostacyclin Production by Cultured Human Vascular Endothelial Cells
Publikationsverlauf
Received 19. April 1993
Accepted after revision 19. August 1993
Publikationsdatum:
06. Juli 2018 (online)
Summary
Elevated plasma homocysteine is associated with an increased risk of intravascular thrombosis. Platelet aggregation and thrombosis are inhibited by prostacyclin produced by the vascular endothelium. Our aim was to investigate whether homocysteine and related metabolites inhibit endothelial prostacyclin production. We used a radioimmunoassay for 6-ketoprostaglandin-F1α to assay medium which had been in contact with confluent cultured endothelial cells. In medium containing 20% human serum, endothelial prostacyclin production was not specifically inhibited by homocysteine, S-adenosylhomocysteine or protein-bound homocysteine. Further, there was no consistent difference in prostacyclin production by cells cultured in medium containing sera from homocystinuria patients, compared with medium containing normal healthy sera. We conclude that vascular disorder in homocystinuria is unlikely to result from effects of homocysteine or related metabolites on endothelial prostacyclin production. By contrast, S-adenosylhomocysteine and protein-bound homocysteine specifically inhibited prostacyclin production by cells cultured in medium containing 20% fetal calf serum.
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References
- 1 Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. In: The Metabolic Basis of Inherited Disease. Scriver CR, Beaudet AL, Sly WS, Valle D. eds 06. th ed. New York: McGraw-HillBook Company; 1989: 693-734
- 2 McCully KS. Vascular pathology of homocysteinemia: implications for the pathology of arteriosclerosis. Am J Pathol 1969; 56: 111-128
- 3 Gibson JB, Carson NAJ, Neil DW. Pathological findings in homocystinuria. J Clin Pathol 1964; 17: 427-437
- 4 Rodgers GM, Conn MT. Homocysteine, an atherogenic stimulus reduces protein C activation by arterial and venous endothelial cells. Blood 1990; 75: 895-901
- 5 Panganamala RV, Karpen CW, Merola AJ. Peroxide mediated effects of homocysteine on arterial prostacyclin synthesis. Prosta Leuko Med 1986; 22: 349-356
- 6 Rodgers GM, Kane WH. Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator. J Clin Invest 1986; 77: 1909-1916
- 7 Bunting S, Gryglewski R, Moncada S, Vane JR. Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac arteries and inhibits platelet aggregation. Prostaglandins 1976; 12: 897-913
- 8 Graeber JE, Slott JH, Ulane RE, Schulman JD, Stuart MJ. Effect of homocysteine and homocystine on platelet and vascular arachidonic acid metabolism. Pediatr Res 1982; 16: 490-493
- 9 Kredich NM, Hershfield MS. S-Adenosylhomocysteine toxicity in normal and adenosine kinase-deficient lymphoblasts of human origin. Proc Natl Acad Sci USA 1979; 76: 2450-2454
- 10 Brattstrom LE, Israelsson B, Jeppsson JO, Hultberg BL. Folic acid – an innocuous means to reduce plasma homocysteine. Scand J Clin Lab Invest 1988; 48: 215-221
- 11 Maciag T, Hoover GA, Stemerman MB, Weinstein R. Factors which stimulate the growth of human umbilical vein endothelial cells in vitro. In: Biology of Endothelial Cells. Jaffe EA. ed Boston: Martinus Nijhoff; 1984: 87-96
- 12 Dudman NPB, Hicks C, Wang J, Wilcken DEL. Human arterial endothelial cell detachment in vitro: its promotion by homocysteine and cysteine. Atherosclerosis 1991; 91: 77-88
- 13 Starkebaum G, Harlan JM. Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest 1986; 77: 1370-1376
- 14 van Asbeck BS, Hoidal J, Vercellotti GM, Schwartz BA, Moldow CF, Jacob HS. Protection against lethal hyperoxia by tracheal insufflation of erythrocytes: role of red cell glutathione. Science 1985; 227: 756-759
- 15 Toth KM, Clifford DP, Berger EM, White CW, Repine JE. Intact human erythrocytes prevent hydrogen peroxide-mediated damage to isolated perfused rat lungs and cultured bovine pulmonary artery endothelial cells. J Clin Invest 1984; 74: 292-295
- 16 Wall RT, Harlan JM, Harker LA, Striker GE. Homocysteine-induced endothelial cell injury in vitro: A model for the study of vascular injury. Thromb Res 1980; 18: 113-121
- 17 Harker LA, Harlan JM, Ross R. Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arterioslcerosis in baboons. Circ Res 1983; 53: 731-739
- 18 Cantoni GL. S-Adenosylmethionine: present status and future perspectives. In: The Biochemistry of Adenosylmethionine. Salvatore F, Borek E, Zappia V, Williams-Ashman HG, Schlenk F. eds New York: Columbia University Press; 1977: 557-577
- 19 Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem 1990; 01: 228-237
- 20 Marcus AJ. Platelet lipids. In: Hemostasis and Thrombosis. Colman RW, Hirsh J, Marder VJ, Salzman EW. eds. Philadelphia: JB Lippincott Company; 1982: 472-485
- 21 Ritter JM, Ongari M-A, Orchard MA, Lewis PJ. Prostacyclin synthesis is stimulated by a serum factor formed during coagulation. Thromb Haemostas 1983; 49: 58-60
- 22 Wiley VC, Dudman NPB, Wilcken DEL. Interrelations between plasma-free and protein-bound homocysteine and cysteine in homocystinuria. Metabolism 1988; 37: 191-195
- 23 Strisciuglio P, Di MinnoG, Margaglione M, Cirillo F, Davi G, Cerbone AM, Grandone E, Lijoi S, Andria G. Monocyte superoxide anion generation and in vivo activation of platelets in homocystinuria. Am J Human Genetic. 1991 49. (suppl): abstract 872
- 24 Fitzgerald GA, Smith B, Pedersen AK, Brash AR. Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. N Engl J Med 1984; 310: 1065-1068