Advertisement

Defective Serum PGI2 Binding in Thrombotic Stroke: A Potential Mechanism for Platelet Hyperaggregability in Stroke

  • K. K. Wu
Conference paper

Abstract

The blood platelet plays a pivotal role in the pathogenesis of thrombotic stroke. It contributes to the formation of atherosclerotic plugs via its interaction with damaged vessel wall and the release of platelet-derived growth factor (PDGF) from its α-granules and generation of 12-hydroxyeicosatetraenoic acid (12-HETE) via arachidonic acid metabolism. 12-HETE induces vascular smooth muscle cell migration [8] while PDGF stimulates its proliferation [12]. Platelets are key elements of thrombotic plugs formed on the atherosclerotic plugs. Formation of thrombotic plugs involves multiple steps of platelet activation including adhesion, spreading, release reaction, and aggregation and the surface catalysis of coagulation. Multiple chemical reactions are activated to initiate and reinforce these biological processes. This subject is beyond the scope of this paper and readers are referred to review articles [19]. It is sufficient to emphasize that thrombotic plugs and the detached debris are the major factors contributing to the acute cerebrovascular events.

Keywords

Stroke Patient Platelet Activation Thrombotic Thrombocytopenic Purpura Maximal Binding Capacity Vascular Smooth Muscle Cell Migration 
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. 1.
    Chen Y-C, McLeod B, Hall ER, Wu KK (1981) Accelerated prostacyclin degradation in thrombotic thrombocytopenic purpura. Lancet II: 267–269CrossRefGoogle Scholar
  2. 2.
    Cho MJ, Allen MA (1978) Chemical stability of prostacyclin in aqueous solutions. Prostagl 15: 943–954CrossRefGoogle Scholar
  3. 3.
    Francesco V, Cesare A, Luigi I etal (1985) Malondialdehyde-like material and betathromboglobulin plasma levels in patients suffering from transient ischemic attacks. Stroke 16: 14–16PubMedCrossRefGoogle Scholar
  4. 4.
    Gimeno MF, Sterlin-Borda L, Borda ES, Lazzari MA, Gimeno AL (1980) Human plasma transforms PGI2 into a platelet antiaggregatory substance which contracts isolated bovine coronary arteries. Prostagl 19: 907–916CrossRefGoogle Scholar
  5. 5.
    Hall JM, Strange PG (1984) The use of a prostacyclin analogue [3H] iloprost for studying prostacyclin binding sites on human platelets. Brosci Rep 4: 941–948CrossRefGoogle Scholar
  6. 6.
    Hummel JP, Dreyer WJ (1962) Measurement of protein-binding phenomena by gel filtration. Biochem Biophys Acta 63: 530–532PubMedCrossRefGoogle Scholar
  7. 7.
    Mikhailidis DP, Mikhailidis AM, Dandona P (1982) Effect of human plasma proteins on stabilization of platelet antiaggregatory activity of PGI2 Ann Clin Bioch 19: 241–244Google Scholar
  8. 8.
    Nakao J, Ooyama T, Ito H etal. (1982) Comparative effect of lipoxygenase products of arachidonic acid on rat aortic smooth muscle cell migration. Atherosclerosis 44: 339–342PubMedCrossRefGoogle Scholar
  9. 9.
    Orchard MA, Robinson C (1981) Stability of prostacyclin in human plasma and whole blood. Studies on the protective effect of albumin. Thromb Haemostasis 46: 645–647Google Scholar
  10. 10.
    Papp AC, Hall ER, Wu KK (1985) Binding of prostacyclin by plasma glycoproteins. Prostagl 30: 1057–1068CrossRefGoogle Scholar
  11. 11.
    Pifer DD, Cagan GLM, Chesney CM (1981) Stability of PGI2 in human blood. Prostagl 21: 165–175CrossRefGoogle Scholar
  12. 12.
    Ross R (1986) The pathogenesis of atherosclerosis an update. N Engl J Med 314: 488–500PubMedCrossRefGoogle Scholar
  13. 13.
    Rücker W, Schrör K (1983) Evidence for high affinity prostacyclin binding sites in vascular tissue: radioligand studies with a chemically stable analog. Biochem Pharmacol 32: 2405–2410PubMedCrossRefGoogle Scholar
  14. 14.
    Shah AB, Beamer N, Coull BM (1985) Enhanced in vivo platelet activation in subtypes of ischemic stroke. Stroke 16: 643–647PubMedCrossRefGoogle Scholar
  15. 15.
    Stein RW, Papp AC, Weiner WJ, Wu KK (1985) Reduction of serum prostacyclin stability in ischemic stroke. Stroke 16: 16–19PubMedCrossRefGoogle Scholar
  16. 16.
    Wong P Y-K, Malik KU, Desiderio DM, McGiff JC, Sun FF (1980) Hepatic metabolism of PGI2 in the rabbit. Formation of a potent novel inhibition of platelet aggregation. Biochem Biophys Res Comm 93: 486–494PubMedCrossRefGoogle Scholar
  17. 17.
    Wu KK, Hoak JC (1975) Increased platelet aggregates in patients with transient ischemic attacks. Stroke 6: 521–524PubMedCrossRefGoogle Scholar
  18. 18.
    Wu KK, Hall ER, Papp AC (1982) Prostacyclin stabilizing factor deficiency in thrombotic thrombocytopenic purpura. Lancet I: 460–461CrossRefGoogle Scholar
  19. 19.
    Wu KK (1984) Thromboembolic disorders. PSG Publishing Company, Littleton, MassachusettsGoogle Scholar
  20. 20.
    Wu KK, Hall ER, Rossi EC, Papp AC (1985) Serum PGI2 binding defects in TTP. J Clin Invest 75: 168–174PubMedCrossRefGoogle Scholar
  21. 21.
    Wynalda MA, Fitzpatrick FA (1980) Albumin stabilizes prostaglandin I2 Prostagl 20: 853–861CrossRefGoogle Scholar
  22. 22.
    Tsai AL, Wu KK (1987) Stabilization of prostacyclin by human serum: an approach by binding kinetics using a stable prostaglandin I2 analogue, iloprost. Biochimica et Biophysica Acta 924: 67–74PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • K. K. Wu
    • 1
  1. 1.Division of Hematology/Oncology, Department of Internal MedicineUniversity of Texas Health Science Center at HoustonHoustonUSA

Personalised recommendations