Advertisement

Prostacyclin and Atherosclerosis—A Hypothesis

  • Ryszard J. Gryglewski
Conference paper

Abstract

In 1976 we discovered (Bunting et al. 1976; Gryglewski et al. 1976; Moncada et al. 1976 a,b) that prostaglandin (PG) endoperoxides are transformed by arterial microsomes to an unstable substance with anti-aggregatory and vasodilator properties. This new lipid factor was called PGX, and when it was later synthesized its name was changed to prostacyclin (PGI2) (Johnson et al. 1976). Prostacyclin spontaneously decomposes to a biologically inactive prostaglandin. In extravasated blood at 37°C the half life of prostacyclin is 3 min (Dusting et al. 1978).

Keywords

Arterial Wall Atherosclerotic Plaque Formation Experimental Atherosclerosis Prostaglandin Endoperoxide Unstable Substance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Angelo V, Myśliwiec M, Donati MB, Gaetan G (1978) Defective fibrynolytic and prostacyclin-like activity in human atheromatous plaques. Thrombos Haemostas 39: 535–536Google Scholar
  2. Bunting S, Gryglewski R, Moncada S, Vane JR (1976) Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac arteries and inhibits platelet aggregation. Prostaglandins 12: 897–913PubMedCrossRefGoogle Scholar
  3. Coffman JD (1979) Drug Therapy: Vasodilator drugs in peripheral vascular diseases. N Engl J Med 300: 713–721PubMedCrossRefGoogle Scholar
  4. De Dekere EAM, Nugteren DH, Ten Hoo F (1977) Prostacyclin is the major metabolite released from the isolated perfused rabbit and rat heart. Nature 268: 160–163CrossRefGoogle Scholar
  5. Dembińska-Kieć A, Gryglewska T, Żmuda A, Gryglewski RJ (1977) The generation of prostacyclin by arteries and by the coronary vascular bed is reduced in experimental atherosclerosis in rabbits. Prostaglandins 14: 1025–1035PubMedCrossRefGoogle Scholar
  6. Dembińska-Kieć A, Rücker W, Schönhofer PS (1979a) Effects of dipyridamole in experimental atherosclerosis: Action of PGI2, platelet aggregation and atherosclerotic plaque formation. Atherosclerosis, in pressGoogle Scholar
  7. Dembińska-Kieć A, Rücker W, Schönhofer PS (1979b) Atherosclerosis decreases prostacyclin synthesis in rabbit lungs and kidneys. Prostaglandins, in pressGoogle Scholar
  8. Dembińska-Kieć A, Rücker W, Schönhofer PS (1979c) Effects of dipyridamole in vivo on ATP and c-AMP content in platelets and arterial walls and on atherosclerotic plaque formation. Naunyn-Schmiedeberg’s Arch Pharmacol, in pressGoogle Scholar
  9. Dusting GJ, Moncada S, Vane JR (1978) Recirculation of prostacyclin (PGI2) in the dog. Br J Pharmacol 63: 315–320Google Scholar
  10. Gorman RR, Bunting S, Miller OV (1977) Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins 13: 377–388PubMedCrossRefGoogle Scholar
  11. Gryglewski RJ, Bunting S, Moncada S, Flower RJ, Vane JR (1976) Arterial walls are protected against deposition of platelet thrombi by a substance (pro-staglandin X) which they make from prostaglandin endoperoxides. Prostaglandins 12: 685–713PubMedCrossRefGoogle Scholar
  12. Gryglewski RJ, Dembinska-Kiec A, Chytkowski A, Gryglewsk T (1978a) Prostacyclin and thromboxane A2 biosynthesis capacities of heart, arteries and platelets at various stages of experimental atherosclerosis in rabbits. Atherosclerosis 31: 385–394PubMedCrossRefGoogle Scholar
  13. Gryglewski RJ, Korbut R, Ocetkiewic A (1978b) Generation of prostacyclin by lungs in vivo and its release into the arterial circulation. Nature 273: 765–767PubMedCrossRefGoogle Scholar
  14. Gryglewski RJ, Korbut R, Ocetkiewic A (1978c) De-aggregatory action of prostacyclin in vivo and its enhancement by theophylline. Prostaglandins 15: 637–644PubMedCrossRefGoogle Scholar
  15. Gryglewski RJ, Korbut R, Ocetkiewicz A, Splawiński J, Wojtaszek B, Świes J (1978d) Lungs as a generator of prostacyclin — hypothesis on physiological significance. Naunyn Schmiede-berg’s Arch Pharmacol 304: 45–50CrossRefGoogle Scholar
  16. Gryglewski RJ, Korbut R, Splawiński J (1979) Endogenous mechanisms which regulate prostacyclin release. Haemostasis, in pressGoogle Scholar
  17. Gryglewski RJ, Szczeklik A, Niźankowski R (1978e) Antiplatelet action of intravenous infusion of prostacyclin in man. Thromb Res 13: 153–163PubMedCrossRefGoogle Scholar
  18. Harker LA, Ross R, Glomse J (1976) Role of the platelet in atherogenesis. Ann NY Acad Sci 275: 321–329PubMedCrossRefGoogle Scholar
  19. Johnson RA, Morton DR, Kinner JH, Gorman RR, McGuire JC, Sun FF, Whittaker N, Bunting S, Salmon J, Moncada S, Vane JR (1976) The chemical structure of prostaglandin X (prostacyclin). Prostaglandins 12: 915–928PubMedCrossRefGoogle Scholar
  20. Moncada S, Gryglewski R, Bunting S, Vane JR (1976a) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663–665PubMedCrossRefGoogle Scholar
  21. Moncada S, Gryglewski RJ, Bunting S, Vane JR (1976b) A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation. Prostaglandins 12: 715–733PubMedCrossRefGoogle Scholar
  22. Moncada S, Herman AG, Hihhs EA, Vane JR (1977) Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for anti-thrombotic properties of vascular endothelium. Thromb Res 11: 323–344Google Scholar
  23. Moncada S, Korbut R, Bunting S, Vane JR (1978) Prostacyclin is a circulating hormone. Nature 273: 767–768PubMedCrossRefGoogle Scholar
  24. Numan F (1977) Progression and regression of atherosclerosis. Asian Med J 20: 625–644Google Scholar
  25. Numano F, Maezawa H, Shimamoto T, Adach K (1976) Changes of cyclic AMP and cyclic AMP phosphodiesterase in the progression and regression of experimental atherosclerosis. Ann NY Acad Sci 275: 311–320PubMedCrossRefGoogle Scholar
  26. Olsson AG, Jogestran T (1978) Effects of prostaglandin E1 in peripheral artery disease. In: Carlson LA, Paoletti R, Sirtori CR, Weber G (eds) Atherosclerosis. Raven Press, New York, pp 403–411Google Scholar
  27. Ross R, Harke L (1976) Hyperlipidemia and atherosclerosis. Science 193: 1094–1100PubMedCrossRefGoogle Scholar
  28. Salmon JA, Smith DR, Flower RJ, Moncada S, Vane JR (1978) Some characteristics of the prostacyclin synthesising enzyme in porcine aorta. Biochim Biophys Acta 523: 250–262PubMedGoogle Scholar
  29. Silberbauer K, Sinzinger H, Winte M (1979) Prostacyclin activity in rat kidney stimulated by angiotensin II. Br J Exp Path 60: 38–44Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1980

Authors and Affiliations

  • Ryszard J. Gryglewski

There are no affiliations available

Personalised recommendations