Abstract
Endothelial cells synthesize prostacyclin (PGI2), an unstable prostaglandin that inhibits platelet aggregation and serotonin release. Because cyclooxygenase, which is necessary for synthesis of PGI2, is inactivated by aspirin, we examined the effect of aspirin on PGI2 production by cultured human endothelial cells. Endothelial cells synthesize PGI2 (20.1±7.2 ng/106 cells, mean±SD) when stimulated with 20 μM sodium arachidonate for 2 min. PGI2 production is inhibited by low-dose aspirin (5 μM); the t½ of inactivation is 6.0±1.3 min (mean±SEM, n = 3). Thus, endothelial cell cyclooxygenase is as sensitive to aspirin as the enzyme in platelets. After 1 h incubation with aspirin, endothelial cell PGI2 production was inhibited 50% by 2.1±0.4 μM aspirin and was inhibited 90% by 6.2±0.9 μM aspirin (mean±SEM, n = 4). When endothelial cells were incubated with 100 μM aspirin, washed, and recultured, their ability to synthesize PGI2 returned to control levels in 35.6±1.0 h (mean±SEM, n = 4). Recovery of endothelial PGI2 production after aspirin depended on de novo protein synthesis because treatment with cycloheximide (3 μg/ml) inhibited recovery by 92%.
These results indicate that although endothelial cell cyclooxygenase in vitro is inhibited by low concentrations of aspirin, endothelial cells rapidly resynthesize their cyclooxygenase after the aspirin is removed. This rapid resynthesis of cyclooxygenase lessens the likelihood that aspirin used in clinical doses promotes thrombosis.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Burch J. W., Stanford N., Majerus P. W. Inhibition of platelet prostaglandin synthetase by oral aspirin. J Clin Invest. 1978 Feb;61(2):314–319. doi: 10.1172/JCI108941. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gorman R. R., Bunting S., Miller O. V. Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins. 1977 Mar;13(3):377–388. doi: 10.1016/0090-6980(77)90018-1. [DOI] [PubMed] [Google Scholar]
- Higgs E. A., Moncada S., Vane J. R., Caen J. P., Michel H., Tobelem G. Effect of prostacyclin (PGI2) on platelet adhesion to rabbit arterial subendothelium. Prostaglandins. 1978 Jul;16(1):17–22. doi: 10.1016/0090-6980(78)90197-1. [DOI] [PubMed] [Google Scholar]
- Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Livio M., Villa S., de Gaetano G. Aspirin, thromboxane, and prostacyclin in rats: A dilemma resolved? Lancet. 1978 Jun 17;1(8077):1307–1307. doi: 10.1016/s0140-6736(78)91286-2. [DOI] [PubMed] [Google Scholar]
- Moncada S., Vane J. R. Unstable metabolites of arachidonic acid and their role in haemostasis and thrombosis. Br Med Bull. 1978 May;34(2):129–135. doi: 10.1093/oxfordjournals.bmb.a071482. [DOI] [PubMed] [Google Scholar]
- Roth G. J., Stanford N., Majerus P. W. Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3073–3076. doi: 10.1073/pnas.72.8.3073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Tateson J. E., Moncada S., Vane J. R. Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins. 1977 Mar;13(3):389–397. doi: 10.1016/0090-6980(77)90019-3. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]