Generation of a PGI₂-Like Activity by Deendothelialized Rat Aorta

Summary

We have tested a platelet aggregation inhibitor in the incubation fluid of deendothelialized fragments of the rat aorta and compared it with that of “intact” fragments. Some of the properties of the aortic inhibitor, and its effects on platelet adhesion to collagen fibrils, on platelet factor-3 (PF-3) availability, and on the activated partial thromboplastin time (APTT) and thrombin time (TT) were also evaluated in comparison with similar effects exerted by PGI₂. We found that the incubation fluid of deendothelialized aortic samples contained inhibitor activity comparable with that of “intact” samples. The aortic inhibitor had similar properties to PGI₂. The aortic inhibitor and PGI₂ slightly inhibited light transmission changes of EDTA-PRP following exposure to collagen. However, scanning electron microscopy showed no appreciable difference in platelet adhesion to collagen fibrils. PGI₂ and the aortic inhibitor inhibited Kaolin-induced PF-3 availability, but did not prolong the APTT or TT.

• References

• 1 Anderson TF. 1951; Techniques for the preservation of three dimensional structure in preparing specimens for electron microscope. Transactions of New York Academy of Science 13: 130
• 2 Baumgartner HR, Haudenschild C. 1972; Adhesion of platelets to subendothelium. Annals of the New York Academy of Sciences 201: 22
• 3 Deykin D. 1967; Thrombogenesis. New England Journal of Medicine 276: 622
• 4 Eisenstein R, Knettner K. 1976; The ground substance of the arterial wall. Part 2. Electron- microscopic studies. Atherosclerosis 27: 37
• 5 Glagov S, Ts’Ao C. 1975; Restitution of aortic wall after sustained necrotizing transmural ligation injury. Role of blood cells and arterial cells American Journal of Pathology 79: 7
• 6 Green D, Dunne B, Schmid RF, Rossi EC, Louis G. 1973; A study of the variable response of human platelets to collagen. Relation to aspirin-induced inhibition of aggregation American Journal of Clinical Pathology 60: 920
• 7 Gryglewski RJ, Bunting S, Moncada S, Flower RJ, Vane JR. 1976; Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins 12: 685
• 8 Hornstra C, Haddeman E, Don JA. 1978; Some investigations into the role of prostacyclin in thromboregulation. Thrombosis Research 12: 367
• 9 Moncada S, Gryglewski R, Bunting S, Vane JR. 1976; An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663
• 10 Moncada S, Higgs EA, Vane JR. 1977; Human arterial and venous tissue generate prostacyclin (prostaglandin X), a potent inhibitor of platelet aggregation. Lancet 1: 18
• 11 Moncada S, Vane JR. 1977. The discovery of prostacyclin - a fresh insight into arachidonic acid metabolism. In Biochemical Aspects of Prostaglandins and Thromboxanes. Academic Press; New York: p 155
• 12 Moncada S, Herman AG, Higgs EA, Vane JR. 1977; Differential formation of prostacyclin (PGX or PGI₂) by layers of the arterial wall. An explanation for the antithrombotic properties of vascular endothelium. Thrombosis Research 11: 323
• 13 Moncada S, Vane JR, Whittle BJ R. 1977; Relative potency of prostacyclin, prostaglandin E₁ and D₂ inhibitors of platelet aggregation in several species. Journal of Physiology (London) 273: 2
• 14 Payling-Wright H. 1971; Areas of mitosis in aortic endothelium of guinea-pigs. Journal of Pathology 105: 65
• 15 Spaet TH, Cintron J. 1965; Studies on platelet factor-3 availability. British Journal of Haematology 11: 269
• 16 Spaet TH, Lejnieks I. 1969; A technique for estimation of platelet collagen adhesion. Proceedings of the Society for Experimental Biology and Medicine 132: 1038
• 17 Stemerman MB. 1974. Vascular intimal components: Precursors of thrombosis. In SPAET TH. (Ed.) Progress in Hemostasis and Thrombosis. Gruñe & Stratton; New York: p 1
• 18 Tansik RL, Namm DH, White HL. 1978; Synthesis of prostaglandin 6-keto-F_lα by cultured aortic smooth muscle cells and stimulation of its formation in a coupled system with platelet lysates. Prostaglandins 15: 399
• 19 Ts’Ao C. 1970; Graded endothelial injury of the rabbit aorta, with special reference to platelet deposition. Archives of Pathology 90: 222
• 20 Ts’Ao C. 1976; Rat platelet aggregation by ATP. Aggregometrical and ultrastructural comparison with aggregations by ADP and collagen American Journal of Pathology 85: 581
• 21 Ts’Ao C. 1979; Vascular substances that modulate blood-to-vessel wall interactions. Artery 5: 246
• 22 Ts’Ao C, Eisenstein E, Schumacher B. 1977; Effect of an aortic proteoglycan on platelet aggregation and thrombin time. Plasma requirement and active moieties Proceedings of the Society for Experimental Biology and Medicine 156: 162
• 23 Villa S, Myslewiec M, Degaetano G. 1977; Prostacyclin and atherosclerosis in rats. Lancet 1: 1216
• 24 Weksler BB, Marcus AJ, Jaffe EA. 1977; Synthesis of prostaglandin I₂ (prostacyclin) by cultured human and bovine endothelial cells. Proceedings of the National Academy of Sciences U.S.A. 74: 3922
• 25 Wight TN, Ross R. 1975; Proteoglycans in primate arteries. I. Ultrastructural localization and distribution in the intima. Journal of Cell Biology 67: 667
• 26 Wilner GD, Nossel HL, Leroy ED. 1968; Activation of Hageman factor by collagen. Journal of Clinical Investigation 47: 2608