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. 1979 May;63(5):1089–1092. doi: 10.1172/JCI109379

Inhibition of prostacyclin by treatment of endothelium with aspirin. Correlation with platelet adherence.

R L Czervionke, J B Smith, G L Fry, J C Hoak, D L Haycraft
PMCID: PMC372053  PMID: 376548

Abstract

Aspirin treatment of cultured endothelial cells from the umbilical vein increased the adherence of 51Cr-platelets when thrombin was present. If the cyclooxygenase activity of endothelium was inhibited by aspirin, as it is in the platelet, reduction of endogenous prostacyclin (PGI2) production could have been responsible. By correlating thrombin-induced adherence of platelets to endothelial monolayers with PGI2 release (as measured by radioimmunoassay for 6-keto-prostaglandin FI1 alpha [6-keto-PGF1 alpha]), we have demonstrated an inverse relationship between platelet adherence and PGI2 levels. Untreated endothelial monolayers exposed to thrombin and platelets resulted in 4% platelet adherence and 107 nM 6-keto-PGF1 alpha. With 0.1 mM aspirin treatment, which is known to block platelet cyclooxygenase, adherence was 5% and 6-keto-PGF1 alpha decreased to 45 nM. Increasing the aspirin concentration to 1 mM resulted in 44% adherence and less than 3 nM 6-keto-PGF1 alpha. When 25 nM exogenous PGI2 was added to 1 mM aspirin-treated endothelium, adherence returned to 5%. The increase in thrombin-induced platelet adherence to 1 mM aspirin-treated monolayers was reversed 2 h after removal of the aspirin solution. 6-Keto-PGF1 alpha returned to 37% of the untreated monolayer value. Recovery from the aspirin effect did not occur when cycloheximide, an inhibitor of protein synthesis, was present during the 2-h period.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baenziger N. L., Dillender M. J., Majerus P. W. Cultured human skin fibroblasts and arterial cells produce a labile platelet-inhibitory prostaglandin. Biochem Biophys Res Commun. 1977 Sep 9;78(1):294–301. doi: 10.1016/0006-291x(77)91253-0. [DOI] [PubMed] [Google Scholar]
  2. Bennett L. L., Jr, Ward V. L., Brockman R. W. Inhibition of protein synthesis in vitro by cycloheximide and related glutarimide antibiotics. Biochim Biophys Acta. 1965 Jul 15;103(3):478–485. doi: 10.1016/0005-2787(65)90140-1. [DOI] [PubMed] [Google Scholar]
  3. Burch J. W., Baenziger N. L., Stanford N., Majerus P. W. Sensitivity of fatty acid cyclooxygenase from human aorta to acetylation by aspirin. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5181–5184. doi: 10.1073/pnas.75.10.5181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Czervionke R. L., Hoak J. C., Fry G. L. Effect of aspirin on thrombin-induced adherence of platelets to cultured cells from the blood vessel wall. J Clin Invest. 1978 Oct;62(4):847–856. doi: 10.1172/JCI109197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Czervionke R. L., Smith J. B., Hoak J. C., Fry G. L., Haycraft D. L. Use of a radioimmunoassay to study thrombin-induced release of PGI2 from cultured endothelium. Thromb Res. 1979;14(4-5):781–786. doi: 10.1016/0049-3848(79)90132-4. [DOI] [PubMed] [Google Scholar]
  6. Gordon J. L., Pearson J. D. Effects of sulphinpyrazone and aspirin on prostaglandin I2 (prostacyclin) synthesis by endothelial cells. Br J Pharmacol. 1978 Dec;64(4):481–483. doi: 10.1111/j.1476-5381.1978.tb17308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kelton J. G., Hirsh J., Carter C. J., Buchanan M. R. Thrombogenic effect of high-dose aspirin in rabbits. Relationship to inhibition of vessel wall synthesis of prostaglandin I2-like activity. J Clin Invest. 1978 Oct;62(4):892–895. doi: 10.1172/JCI109203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. MacIntyre D. E., Pearson J. D., Gordon J. L. Localisation and stimulation of prostacyclin production in vascular cells. Nature. 1978 Feb 9;271(5645):549–551. doi: 10.1038/271549a0. [DOI] [PubMed] [Google Scholar]
  9. Maca R. D., Fry G. L., Hakes A. D. Effects of glucocorticoids on the interaction of lymphoblastoid cells with human endothelial cells in vitro. Cancer Res. 1978 Aug;38(8):2224–2228. [PubMed] [Google Scholar]
  10. Marcus A. J., Weksler B. B., Jaffe E. A. Enzymatic conversion of prostaglandin endoperoxide H2 and arachidonic acid to prostacyclin by cultured human endothelial cells. J Biol Chem. 1978 Oct 25;253(20):7138–7141. [PubMed] [Google Scholar]
  11. Moncada S., Herman A. G., Higgs E. A., Vane J. R. Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for the anti-thrombotic properties of vascular endothelium. Thromb Res. 1977 Sep;11(3):323–344. doi: 10.1016/0049-3848(77)90185-2. [DOI] [PubMed] [Google Scholar]
  12. Nordøy A., Svensson B., Hoak J. C. The inhibitory effect of human endothelial cell monolayers on platelet reactions and its inhibition by aspirin. Thromb Res. 1978 Apr;12(4):597–608. doi: 10.1016/0049-3848(78)90249-9. [DOI] [PubMed] [Google Scholar]
  13. Rowland M., Riegelman S., Harris P. A., Sholkoff S. D. Absorption kinetics of aspirin in man following oral administration of an aqueous solution. J Pharm Sci. 1972 Mar;61(3):379–385. doi: 10.1002/jps.2600610312. [DOI] [PubMed] [Google Scholar]
  14. Villa S., de Gaetano G. Prostacyclin-like activity in rat vascular tissues. Fast, long-lasting inhibition by treatment with lysine acetylsalicylate. Prostaglandins. 1977;14(6):1117–1124. doi: 10.1016/0090-6980(77)90289-1. [DOI] [PubMed] [Google Scholar]
  15. Weksler B. B., Ley C. W., Jaffe E. A. Stimulation of endothelial cell prostacyclin production by thrombin, trypsin, and the ionophore A 23187. J Clin Invest. 1978 Nov;62(5):923–930. doi: 10.1172/JCI109220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Weksler B. B., Marcus A. J., Jaffe E. A. Synthesis of prostaglandin I2 (prostacyclin) by cultured human and bovine endothelial cells. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3922–3926. doi: 10.1073/pnas.74.9.3922. [DOI] [PMC free article] [PubMed] [Google Scholar]

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