Skip to main content
SpringerLink
Log in

Prostaglandine und Atherosklerose

  • Chapter
Prostaglandin E1

Zusammenfassung

Für die Entstehung und Progression atherosklerotischer Gefäßwandveränderungen wird heute eine gestörte Interaktion zwischen Gefäßwand (Endothel, glatte Muskelzellen) und Zellen des strömenden Blutes (Thrombozyten, Makrophagen) als entscheidend angesehen [56]. Eine Hyperreaktivität der Thrombozyten mit Adhäsion an der Gefäßwand und Sekretion von Inhaltsstoffen ist dabei ein initialer Vorgang [4]. Fehlen Thrombozyten oder wird ihre Aktivierung pharmakologisch verhindert, dann treten im Tierversuch Proliferationen der Gefäßintima nicht auf [26] und die Progression der atherosklerotischen Gefäßwand-veränderungen wird verzögert [27]. Hierbei ist die Freisetzung mitogener Faktoren aus Plättchen sowie Makrophagen und eventuell dem geschädigten Endothel entscheidend für die Proliferation der glatten Muskelzellen, die ebenfalls mitogene Faktoren bilden können [63]. Unabhängig von den im einzelnen noch unklaren pathogenetischen Zusammenhängen kann daher angenommen werden, daß aktivierte Thrombozyten nicht nur entscheidend für die akuten thromboembolischen Komplikationen der Atherosklerose (Myocardinfarkt, Schlaganfall, Verschluß peripherer Gefäße) sind, sondern auch zur Entstehung und Progression der Erkrankung beitragen.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 54.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. Änggard E (1966) The biological activity of three metabolites of Prostaglandin E1. Acta Physiol Scand 66: 509–510

    Article  PubMed  Google Scholar 

  2. Antiplatelet trialists’ collaboration (1988) Secondary prevention of vascular disease by prolonged antiplatelet treatment. Br Med J 296: 320–331

    Article  Google Scholar 

  3. Belch JJF, Cormie J, Newman P, McLaren M, Barbenel J, Capell H, Lieberman P, Forbes CD, Prentice CRM (1983) Dazoxiben, a thromboxane synthetase inhibitor, in the treatment of Raynaud’s Syndrome: A double blind trial. Br J Clin Pharmacol 15: 1135–1165

    Article  Google Scholar 

  4. Benner KU, Geeren M, Burstedde V, Everts B (1984) Platelet aggregation abnormalities in arterial occlusive diseases. J Med 15: 23–34

    CAS  PubMed  Google Scholar 

  5. Bertele V, Falanga A, Tomasiak M, Chiabrando C, Cerletti C, de Gaetano G (1984) Pharamcological inhibition of thromboxane synthetase and platelet aggregation: modulatory role of cyclooxygenäse products. Blood 63: 1460–1466

    CAS  Google Scholar 

  6. Bertele V, Falanga A, Tomasiak M, Dejana E, Cerletti C, de Gaetano G (1983) Platelet thromboxane synthetase inhibitors with low doses of aspirin: Possible resolution of the “Aspirin Dilemma”. Science 220: 517–519

    Article  CAS  PubMed  Google Scholar 

  7. Brecht Th, Ayaz M (1985) Circulation parameters during intravenous and intraarterial administration of increasing doses of Prostaglandin Et in healthy subjects. Klin Wschr. 63: 1201–1204

    Article  CAS  PubMed  Google Scholar 

  8. Coffman JD, Rasmussen HM (1984) Effect of thromboxane synthetase inhibition in Raynaud’s phenomenon. Clin Pharmacol Ther 36: 373

    Article  Google Scholar 

  9. Cowley AJ, Jones EW, Hanley SP (1984) Effects of dazoxiben, an inhibitor of thromboxane synthetase, on forearm vasoconstriction in response to cold Stimulation and human blood vessel prostacyclin production. Br J Clin Pharmacol 15: 1075–1125

    Google Scholar 

  10. Cox JW, Andreadis NA, Bone RC, Maunder RJ, Pullen RH, Ursprung JJ, Vassar MJ (1988) Pulmonary extraction and pharmacokinetics of Prostaglandin Ej during continuous intravenous infusion in patients with adult respiratory distress Syndrome. Am Rev Resp Dis 137: 5–12

    Article  CAS  PubMed  Google Scholar 

  11. Darius H, Hossmann V, Schrör K (1986) Antiplatelet and blood pressure lowering effects of iloprost in patients with peripheral arterial obliterative disease: A placebo-controlled dose-response study. Klin Wschr 64: 545–551

    Article  CAS  PubMed  Google Scholar 

  12. Dembinska-Kiec A, Gryglewska T, Zmuda A, Gryglewski RJ (1977) The generation of prostacyclin by arteries and by the coronary vascular bed is reduced in experimental atherosclerosis. Prostaglandins 14: 1025–1034

    Article  CAS  PubMed  Google Scholar 

  13. Diehm C, Stammler F, Hübsch C, Eckstein HH (1987) Behandlung von Ruheschmerzen bei peripherer arterieller Verschlußkrankheit ( PAVK) mit intravenösen Prostaglandin-Infusionen. Vasa Suppl 20: 204–205

    Google Scholar 

  14. Eklund AE, Erikson G, Olsson GA (1982) A controlled study showing significant short-term effect of Prostaglandin Ej in healing of ischaemic ulcers in the lower limb in man. Prostaglandins Leukotr Med 8: 265–276

    Article  CAS  Google Scholar 

  15. Fitscha P, Kaliman J, Sinzinger H (1985) Gamma-camera imaging after autologous human platelet labeling with in In-oxine-sulfate: A key for assessing the efficacy of prostacyclin treatment in active atherosclerosis? In: Prostaglandins and other eicosanoids in the cardio-vascular system, K. Schrör (ed), Karger Basel, pp. 352–357

    Google Scholar 

  16. Fitz Gerald GA, Smith B, Pedersen AK, Brash AR (1984) Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. New Engl J Med 310: 1065–1068

    Article  CAS  Google Scholar 

  17. Frishman WH, Christodoulou J, Weksler BB, Smithen C, Killip T, Scheidt S (1976) Aspirin therapy in angina pectoris: effects on platelet aggregation, exercise tolerance, and echo-cardiographic manifestations of ischemia. Am Heart J 92: 3–10

    Article  CAS  PubMed  Google Scholar 

  18. Gillis CN, Pitt BR, Wiedemann P, Hammond GL (1986) Depressed Prostaglandin Et and 5-hydroxytryptamine removal in patients with adult respiratory distress Syndrome. Am Rev Resp Dis 134: 739–744

    CAS  PubMed  Google Scholar 

  19. Goldyne ME, Stobo JD (1981) Immunoregulatory role of Prostaglandins and related lipids. CRC Critical Reviews Immunol 189

    Google Scholar 

  20. Golub M, Zia P, Matsuno M, Horton R (1975) Metabolism of Prostaglandin A] and Et in man. J Clin Invest 56: 1404–1410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Granström E (1967) On the metabolism of Prostaglandin Ej in man. Prostaglandins and related factors 50. Progr Biochem Pharmacol 3: 89–93

    Google Scholar 

  22. Gresele P, Arnout J, Janssens W, Deckmyn H, Lemmens J, Vermylen J (1984) BM 13. 177, a selective blocker of platelet and vessel wall thromboxane receptors, is active in man. Lancet 1: 991–993

    CAS  PubMed  Google Scholar 

  23. Hadjiagapiou C, Spector AA (1986) 12-hydroxyeicosatetraenoic acid reduces prostacyclin production by endothelial cells. Prostaglandins 31: 1135–1144

    Google Scholar 

  24. Hajjar DP, Weksler BB, Falcone DJ, Hefton IM, Tack-Goldman K, Minick CR (1982) Prostacyclin modulates cholesteryl ester hydrolytic activity by its effect on cyclic adenosine monophosphate in rabbit aortic smooth muscle cells. J Clin Invest 70: 479–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hammarström S, Örning L, Bernström K (1985) Metabolism of Leukotrienes. Mol Cell Biochem 69: 7–16

    Article  PubMed  Google Scholar 

  26. Harker LA, Harlan JM, Ross R (1983) Effect of sulfinpyrazone on homocysteine-induced endothelial injury and atherosclerosis in baboons. Circ Res 53: 731–739

    Article  CAS  PubMed  Google Scholar 

  27. Hess H, Mietaschk A, Deichsel G (1985) Drug-induced inhibition of platelet function delays Progression of peripheral occlusive arterial disease. Lancet 1: 415–419

    Article  CAS  PubMed  Google Scholar 

  28. Hirsh PD, Campbell WB, Willerson JT, Hillis LD (1981) Prostaglandins in ischemic heart disease. Am J Med 71: 1009–1015

    Article  CAS  PubMed  Google Scholar 

  29. Hossmann V, Auel H, Rücker W, Schrör K (1984) Prolonged infusion of prostacyclin in patients with advanced stages of peripheral vascular disease: A placebo-controlled crossover study. Klin Wschr 62: 1108–1114

    Article  CAS  PubMed  Google Scholar 

  30. Hossmann V, Heinen A, Auel H, FitzGerald GA (1981) A randomized, placebo-controlled trial of prostacyclin (PGI2) in peripheral arterial disease. Thromb Res 22: 481–490

    Article  Google Scholar 

  31. Humes JL, Opas EE, Galavage M, Soderman D, Bonney RJ (1986) Regulation of macrophage eicosanoid production by hydroperoxy-and hydroxyeicosatetraenoic acids. Biochem J 233: 199–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jakubowski JA, Stampfer MJ, Vaillancourt R, Faigel D, Deykin D (1986) Low-dose enteric coated aspirin: a practical approach to continuous-release low-dose aspirin and presystemic acetylation of human platelet cyclooxygenäse. J Lab Clin Med 108: 616–621

    CAS  PubMed  Google Scholar 

  33. Kannel WB, Castelli WP, Gordon T, McNamara PM (1971) Serum cholesterol, lipoprotein and the risk of coronary heart disease. The Framingham Study. Ann Int Med 74: 1–12

    Article  CAS  PubMed  Google Scholar 

  34. Jaschonek K, Weisenberger H, Karsch KR, Renn W, Daiss W, Schenzle D, Ostendorf P (1984) Impaired platelet prostacyclin binding in acute myocardial infarction. Lancet 2: 1341

    Article  Google Scholar 

  35. Jones EW, Hawkey CJ (1983) A thromboxane synthetase inhibitor in Raynaud’s phenomenon. Prostaglandins Leukotrienes Med 12: 67–71

    Article  CAS  Google Scholar 

  36. Krone W, Kaczmarczyk P, Müller-Wieland D, Greten H (1985) The prostacyclin analogue iloprost and Prostaglandin Ej suppress cholesterol synthesis in freshly isolated human mononuclear leukocytes. Biochim Biophys Acta 835: 154–157

    Article  CAS  PubMed  Google Scholar 

  37. Lagarde M, Dechavanne M (1977) Increase of platelet Prostaglandin cyclic endoperoxides in thrombosis. Lancet 1: 88

    Article  CAS  PubMed  Google Scholar 

  38. Leaf A, Weber PC (1988) Cardiovascular effects of n-3 fatty acids. New Engl J Med 318: 549–557

    Article  CAS  PubMed  Google Scholar 

  39. Lipid Research Clinics Program: The Lipid Research Clinics Coronary primary Prevention Trials Results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 251: 365–374

    Google Scholar 

  40. Löbel P, Steinhagen-Thiessen E, Schrör K (1988) Cholestyramine treatment of type IIa hypercholesterolaemia normalizes platelet reactivity against prostacyclin. Eur J Clin Invest 18: 256–260

    Article  PubMed  Google Scholar 

  41. Löbel P, Steinhagen-Thiessen E, Schrör K (1987) Synvinolin reduces platelet thromboxane (TX) formation and improves PGI2 sensitivity in FH patients. Circulation 76: 1918

    Google Scholar 

  42. Mayer B, Moser R, Gleispach H, Kukovetz WR (1986) Possible inhibitory function of endogenous 15-hydroperoxyeicosatetraenoic acid on prostacyclin formation in bovine aortic endothelial cells. Biochim Biophys Acta 875: 641–653

    Article  CAS  PubMed  Google Scholar 

  43. Mathur SN, Field FJ, Spector AA, Armstrong ML (1985) Increased production of lipo-xygenase products by cholesterol-rich mouse macrophages. Biochim Biophys Acta 837: 13–19

    Article  CAS  PubMed  Google Scholar 

  44. Mehta J, Mehta P, Lawson DL, Ostrowski N, Brigmon L (1985) Influence of selective thromboxane synthetase blocker CGS-13080 on thromboxane and prostacyclin biosynthesis in whole blood: Evidence for synthesis of prostacyclin by leukocytes from platelet-derived endoperoxides. J Lab Clin Med 106: 246–252

    CAS  PubMed  Google Scholar 

  45. Menys VC, Davies JA (1983) Selective inhibition of thromboxane synthetase with dazo-xiben-basis of its inhibitory effect on platelet adhesion. Thromb Haemostas (Stuttgart) 49: 96–101

    CAS  Google Scholar 

  46. Moncada S (1982) Prostacyclin and arterial wall biology. Arteriosclerosis 2: 193–207

    Article  CAS  PubMed  Google Scholar 

  47. Nakano J (1971) Effects of the metabolites of Prostaglandin Et of the systemic and peri-pheral circulations in dogs. Proc Soc Exp Biol Med 136: 1265–1268

    Article  CAS  PubMed  Google Scholar 

  48. Nawroth PP, Stern DM, Kaplan KL, Nossel HL (1984) Prostacyclin production by perturbed bovine aortic endothelial cells in culture. Blood 64: 801

    CAS  PubMed  Google Scholar 

  49. Orekhov AN, Tertov VV, Smirnov VN (1983) Prostacyclin analogues as antiatherosclerotic drugs. Lancet 2: 527

    Google Scholar 

  50. Patscheke H, Staiger C, Neugebauer G, Stegmeier K (1985) Inhibition of platelet activation in man by the selective thromboxane receptor antagonist BM 13. 177. In: Schrör K (Hrsg): Prostaglandins and other Eicosanoids in the Cardiovascular System, pp 504–508. Karger, Basel

    Google Scholar 

  51. Peto R, Gray R, Collins R, Wheatley K, Hennekens C, Jamrozik K, Warlow C, Hafner B, Thompson E, Norton S, Gilliland J, Doli R (1988) Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J 296: 313–316

    Article  CAS  Google Scholar 

  52. Philp RB, Paul ML (1983) Low-dose aspirin (ASA) renders human platelets more vulnerable to inhibition of aggregation by prostacyclin (PGI2). Prostagl Leukotr Med 11: 131

    Article  CAS  Google Scholar 

  53. Poole JCF, Florey HW (1958) Changes in endothelium of the aorta and the behaviour of macrophages in experimental atheroma of the rabbit. J Path Bacteriol 75: 245–252

    Article  CAS  Google Scholar 

  54. Richards CF, Johnson AR, Campbell WB (1986) Specific incorporation of 5-hydroxy-6,8,11,14-eicosatetraenoic acid into phosphatidylcholine in human endothelial cells. Biochim Biophys Acta 875: 569–581

    Article  CAS  PubMed  Google Scholar 

  55. Rolland PH, Jouve R, Pellegrin E, Mercier C, Serradigmini A (1984) Alteration in prostacyclin and Prostaglandin E2 production. Correlation with changes in human aortic athe-rosclerotic disease. Arteriosclerosis 4: 70–78

    Article  CAS  PubMed  Google Scholar 

  56. Ross R (1986) The pathogenesis of atherosclerosisan update. New Engl J Med 314: 488–500

    Article  CAS  PubMed  Google Scholar 

  57. Saito H, Salmon JA, Moncada S (1986) Influence of cholesterol feeding on the production of eicosanoids, tissue Plasminogen activator and Superoxide anion (02-) by rabbit blood monocytes. Atherosclerosis 61: 141–148

    Article  CAS  PubMed  Google Scholar 

  58. Saldeen P, Nilsson IM, Saldeen T (1983) Increased synthesis of thromboxane and PGF2a in veins of patients with deep venous thrombosis. Thromb Res 32: 461–467

    Article  CAS  PubMed  Google Scholar 

  59. Schafer AI, Takayama H, Farrell S, Gimbrone MA (1986) Incorporation of platelet and leukocyte lipoxygenase metabolites by cultured vascular cells. Blood 67: 373–378

    CAS  PubMed  Google Scholar 

  60. Schrey A (Hrsg) (1985) Prostaglandin Et. Therapie der arteriellen Verschlußkrankheit. Wolf & Sohn, München

    Google Scholar 

  61. Schrör K, Latta G, Seidel H, Smith EF III, Palmer M (1986) Thromboxane and prostacyclin generation in hearts, platelets and aorta of cholesterolfed rabbits in relation to platelet function. Naunyn-Schmiedeberg’s Arch Pharmacol 332:R 35

    Google Scholar 

  62. Schrör K, Hecker G (1987) Potent inhibition of Superoxide anion generation by PGEt and the PGE1 analogue OP-1206 in human PMN’s-unrelated to its antiplatelet PGI2-like activity. VASA, Suppl 17, 11–16

    PubMed  Google Scholar 

  63. Schwartz SM, Reidy MA (1987) Common mechanisms of proliferation of smooth muscle in atherosclerosis and hypertension. Human Pathol 18: 240–247

    Article  CAS  Google Scholar 

  64. Shattil SJ, Anaya-Galiudo R, Bennett J et al (1975) Platelet hypersensitivity induced by cholesterol incorporation. J Clin Invest 55: 636–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Simmet Th, Peskar BA, Wolf HRD (1986) On the metabolism of Prostaglandin E, in patients suffering from arterial occlusive disease. In: Prostaglandin Ej in Atherosclerosis, Sinzinger H, Rogatti W (eds) Springer Berlin-Heidelberg-New York, pp 8–12

    Google Scholar 

  66. Sinzinger H, Matejka M, Steurer G, Kaliman J, Ettl K (1986) The interaction between the platelet-derived growth factor (PDGF) and Prostaglandin (PG)I2 is important for athero-genesis. Abstr 6th International Conference on Prostaglandins, p 14

    Google Scholar 

  67. Sinzinger H, Silberbauer K, Feigl W, Wagner O, Winter M, Auerswald W (1979) Prostacyclin activity is diminished in different types of morphologically controlled human atherosclerotic lesions. Thromb Haemostasis 42: 803–804

    CAS  Google Scholar 

  68. Sinzinger H, Silberbauer K, Horsch AK, Gall A (1981) Decreased sensitivity of human platelets to PGI2 during long-term intraarterial prostacyclin infusion in patients with peripheral vascular disease-a rebound phenomenon? Prostaglandins 21: 49–51

    Article  CAS  PubMed  Google Scholar 

  69. Sinzinger H, Silberbauer K, Winter M (1979) Effects of experimental atherosclerosis on prostacyclin (PGI2) generation in arteries of the miniature swine. Artery 5: 448–457

    CAS  Google Scholar 

  70. Smith DL, Willis AL, Nguyen N, Dave S, Yih R, Nakamura G (1986) Antiatherosclerotic properties of prostacyclins on release of mitogens from platelets and endothelial cells. Excerpta Medica Intern Cong Ser 696: 453–456

    CAS  Google Scholar 

  71. Steering Committee of the physicians’ health study research group (1988). Preliminary report: Findings from the aspirin component of the ongoing physicians’ health study. New Engl J Med 318: 262–264

    Article  Google Scholar 

  72. Stuart MJ, Gerrard JM, White JG (1980) Effect of cholesterol on production of throm-boxane B2 by platelets in vitro. New Engl J Med 302: 6–10

    Article  CAS  PubMed  Google Scholar 

  73. Tertov VV, Orekhov AN, Repin VS, Smirnov VN (1982) Biochem Biophys Res Comm 109: 1228–1233

    Article  CAS  PubMed  Google Scholar 

  74. Thaulow E, Dale J, Myhre E (1984) Effects of a selective thromboxane synthetase inhibitor, dazoxiben, and acetylsalicylic acid on myocardial ischemia in patients with coronary artery disease. Am J Cardiol 53: 1255–1258

    Article  CAS  PubMed  Google Scholar 

  75. Trübestein G, Ludwig M, Diehm C, Gruß JD, Horsch S (1987) Prostaglandin Et bei arterieller Verschlußkrankheit im Stadium III und IV. Dtsch Med Wschr 112: 955–959

    Article  PubMed  Google Scholar 

  76. Tyler HM, Saxton CAPD, Parry MJ (1981) Administration to man of UK-37,248-01, a selective inhibitor of thromboxane synthetase. Lancet 1: 629–632

    Article  CAS  PubMed  Google Scholar 

  77. Tyler HM (1983) Dazoxiben: a pharmacological tool or clinical candidate. Br J Clin Pharmacol 79: 953–964

    Article  Google Scholar 

  78. Verheggen R, Schrör K (1986) The modification of platelet-induced coronary vasocon-striction by a thromboxane receptor antagonist. J Cardiovasc Pharmacol 8: 483–490

    Article  CAS  PubMed  Google Scholar 

  79. Voss R, Don JA, Ten Hoor F (1983) Prostacyclin formation by the rabbit aorta: Relation to atherosclerosis. Prostaglandins Leukotrienes Med 11: 451–456

    Article  CAS  Google Scholar 

  80. Westwick J (1976) The effect of pulmonary metabolites of Prostaglandins E1 E2 and F2a on ADP-induced aggregation of human and rabbit platelets. Proc Br Pharmacol Soc, July 15–16, 297P

    Google Scholar 

  81. Wilkens JH, Wilkens H, Elger B, Cassidy F, Caspary L, Creutzig A, Frölich JC (1987) Cardiac and microcirculatory effects of different doses of Prostaglandin Et in man. Eur J Clin Pharmacol 33: 133–137

    Article  CAS  PubMed  Google Scholar 

  82. Willis AL, Smith DL, Vigo C, Kluge AF (1986) Effects of prostacyclin and orally active stable mimetic agent RS-93427-007 on basic mechanisms of atherogenesis. Lancet II: 682–683

    Google Scholar 

Download references

Authors
  1. K. Schrör
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Innere Abteilung, Franziskus-Krankenhaus, Burggrafenstraße 1, 1000, Berlin 30, Germany

    H. Heidrich

  2. Institut für Gefäßerkrankungen, Zentralkrankenhaus Gauting, Unterbrunner Straße 85, 8035, Gauting, Germany

    H. Böhme

  3. Med. Abteilung, Schwarz Pharma GmbH, Mittelstraße 11-13, 4019, Monheim, Germany

    Waltraud Rogatti

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Schrör, K. (1988). Prostaglandine und Atherosklerose. In: Heidrich, H., Böhme, H., Rogatti, W. (eds) Prostaglandin E1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73943-9_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-73943-9_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73944-6

  • Online ISBN: 978-3-642-73943-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation