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. 1990 Dec;86(6):1885–1891. doi: 10.1172/JCI114920

Increased hydrolysis of cholesteryl ester with prostacyclin is potentiated by high density lipoprotein through the prostacyclin stabilization.

H Morishita 1, Y Yui 1, R Hattori 1, T Aoyama 1, C Kawai 1
PMCID: PMC329822  PMID: 2174909

Abstract

Prostacyclin (PGI2) has been reported to stimulate activities of acid cholesteryl ester hydrolase (ACEH; EC 3.1.1.13) and neutral cholesteryl ester hydrolase (NCEH; EC 3.1.1.13) in the smooth muscle cells leading to a decrease in intracellular cholesteryl ester. Recently, we have found that the half-life of PGI2 was prolonged through stabilization by HDL. HDL is known to have anti-atherogenic properties, although its precise mechanism has not been fully clarified. We therefore hypothesized that HDL can exert anti-atherogenic action by augmenting PGI2-stimulated increases in the activities of ACEH and NCEH. After incubation with PGI2 and HDL, a cell homogenate was made from which the activities of ACEH and NCEH were assessed. HDL significantly augmented the PGI2-induced increase in the activities of both enzymes. This effect of HDL was abolished in the absence of PGI2. Elevated intracellular levels of cyclic AMP were maintained for longer periods by HDL. The increase in both intracellular cyclic AMP levels and enzyme activities disappeared in the presence of an inhibitor of adenylate cyclase, 2'5'-dideoxyadenosine. Radiolabeled smooth muscle cells demonstrated a significant loss in total cholesterol and cholesteryl ester after treatment with PGI2 and HDL, due to the increase in cholesteryl ester hydrolytic activities. These data suggest that HDL enhanced the PGI2-stimulated hydrolysis of cholesteryl ester and augmented the PGI2-induced reduction of cellular cholesteryl ester content by stabilizing PGI2.

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Selected References

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

  1. Aoyama T., Yui Y., Morishita H., Kawai C. Prostaglandin I2 half-life regulated by high density lipoprotein is decreased in acute myocardial infarction and unstable angina pectoris. Circulation. 1990 Jun;81(6):1784–1791. doi: 10.1161/01.cir.81.6.1784. [DOI] [PubMed] [Google Scholar]
  2. Brown M. S., Ho Y. K., Goldstein J. L. The cholesteryl ester cycle in macrophage foam cells. Continual hydrolysis and re-esterification of cytoplasmic cholesteryl esters. J Biol Chem. 1980 Oct 10;255(19):9344–9352. [PubMed] [Google Scholar]
  3. Evensen S. A., Blomhoff J. P., Nilsen E., Holme R., Letnes H. Effect of high-density lipoproteins on cholesterol efflux and esterification in lipid-enriched human skin fibroblasts. Scand J Gastroenterol Suppl. 1985;107:61–66. doi: 10.3109/00365528509099754. [DOI] [PubMed] [Google Scholar]
  4. Fleisher L. N., Tall A. R., Witte L. D., Miller R. W., Cannon P. J. Stimulation of arterial endothelial cell prostacyclin synthesis by high density lipoproteins. J Biol Chem. 1982 Jun 25;257(12):6653–6655. [PubMed] [Google Scholar]
  5. Gordon D. J., Knoke J., Probstfield J. L., Superko R., Tyroler H. A. High-density lipoprotein cholesterol and coronary heart disease in hypercholesterolemic men: the Lipid Research Clinics Coronary Primary Prevention Trial. Circulation. 1986 Dec;74(6):1217–1225. doi: 10.1161/01.cir.74.6.1217. [DOI] [PubMed] [Google Scholar]
  6. Green M. S., Heiss G., Rifkind B. M., Cooper G. R., Williams O. D., Tyroler H. A. The ratio of plasma high-density lipoprotein cholesterol to total and low-density lipoprotein cholesterol: age-related changes and race and sex differences in selected North American populations. The Lipid Research Clinics Program Prevalence Study. Circulation. 1985 Jul;72(1):93–104. doi: 10.1161/01.cir.72.1.93. [DOI] [PubMed] [Google Scholar]
  7. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hajjar D. P., Marcus A. J., Etingin O. R. Platelet-neutrophil-smooth muscle cell interactions: lipoxygenase-derived mono- and dihydroxy acids activate cholesteryl ester hydrolysis by the cyclic AMP dependent protein kinase cascade. Biochemistry. 1989 Oct 31;28(22):8885–8891. doi: 10.1021/bi00448a030. [DOI] [PubMed] [Google Scholar]
  9. Hajjar D. P., Minick C. R., Fowler S. Arterial neutral cholesteryl esterase. A hormone-sensitive enzyme distinct from lysosomal cholesteryl esterase. J Biol Chem. 1983 Jan 10;258(1):192–198. [PubMed] [Google Scholar]
  10. Hajjar D. P. Regulation of neutral cholesteryl esterase in arterial smooth muscle cells: stimulation by agonists of adenylate cyclase and cyclic AMP-dependent protein kinase. Arch Biochem Biophys. 1986 May 15;247(1):49–56. doi: 10.1016/0003-9861(86)90531-x. [DOI] [PubMed] [Google Scholar]
  11. Hajjar D. P., Weksler B. B., Falcone D. J., Hefton J. M., Tack-Goldman K., Minick C. R. Prostacyclin modulates cholesteryl ester hydrolytic activity by its effect on cyclic adenosine monophosphate in rabbit aortic smooth muscle cells. J Clin Invest. 1982 Sep;70(3):479–488. doi: 10.1172/JCI110639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hajjar D. P., Weksler B. B. Metabolic activity of cholesteryl esters in aortic smooth muscle cells is altered by prostaglandins I2 and E2. J Lipid Res. 1983 Sep;24(9):1176–1185. [PubMed] [Google Scholar]
  13. Haley N. J., Fowler S., de Duve C. Lysosomal acid cholesteryl esterase activity in normal and lipid-laden aortic cells. J Lipid Res. 1980 Nov;21(8):961–969. [PubMed] [Google Scholar]
  14. Ho Y. K., Brown M. S., Goldstein J. L. Hydrolysis and excretion of cytoplasmic cholesteryl esters by macrophages: stimulation by high density lipoprotein and other agents. J Lipid Res. 1980 May;21(4):391–398. [PubMed] [Google Scholar]
  15. Hojnacki J. L., Smith S. C. Separation of six lipid classes on one thin-layer chromatogram. J Chromatogr. 1974 Apr 10;90(2):364–367. doi: 10.1016/s0021-9673(00)92542-1. [DOI] [PubMed] [Google Scholar]
  16. Khoo J. C., Mahoney E. M., Steinberg D. Neutral cholesterol esterase activity in macrophages and its enhancement by cAMP-dependent protein kinase. J Biol Chem. 1981 Dec 25;256(24):12659–12661. [PubMed] [Google Scholar]
  17. Krieger M., Brown M. S., Faust J. R., Goldstein J. L. Replacement of endogenous cholesteryl esters of low density lipoprotein with exogenous cholesteryl linoleate. Reconstitution of a biologically active lipoprotein particle. J Biol Chem. 1978 Jun 25;253(12):4093–4101. [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. Miller G. J., Miller N. E. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet. 1975 Jan 4;1(7897):16–19. doi: 10.1016/s0140-6736(75)92376-4. [DOI] [PubMed] [Google Scholar]
  20. Miller N. E., La Ville A., Crook D. Direct evidence that reverse cholesterol transport is mediated by high-density lipoprotein in rabbit. Nature. 1985 Mar 7;314(6006):109–111. doi: 10.1038/314109a0. [DOI] [PubMed] [Google Scholar]
  21. Norum R. A., Lakier J. B., Goldstein S., Angel A., Goldberg R. B., Block W. D., Noffze D. K., Dolphin P. J., Edelglass J., Bogorad D. D. Familial deficiency of apolipoproteins A-I and C-III and precocious coronary-artery disease. N Engl J Med. 1982 Jun 24;306(25):1513–1519. doi: 10.1056/NEJM198206243062503. [DOI] [PubMed] [Google Scholar]
  22. Pittman R. C., Khoo J. C., Steinberg D. Cholesterol esterase in rat adipose tissue and its activation by cyclic adenosine 3':5'-monophosphate-dependent protein kinase. J Biol Chem. 1975 Jun 25;250(12):4505–4511. [PubMed] [Google Scholar]
  23. Pomerantz K. B., Tall A. R., Feinmark S. J., Cannon P. J. Stimulation of vascular smooth muscle cell prostacyclin and prostaglandin E2 synthesis by plasma high and low density lipoproteins. Circ Res. 1984 May;54(5):554–565. doi: 10.1161/01.res.54.5.554. [DOI] [PubMed] [Google Scholar]
  24. Portman O. W. Arterial composition and metabolism: esterified fatty acids and cholesterol. Adv Lipid Res. 1970;8:41–114. [PubMed] [Google Scholar]
  25. Ross R. The smooth muscle cell. II. Growth of smooth muscle in culture and formation of elastic fibers. J Cell Biol. 1971 Jul;50(1):172–186. doi: 10.1083/jcb.50.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schmitz G., Robenek H., Beuck M., Krause R., Schurek A., Niemann R. Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. I. Characterization of cellular lipid metabolism. Arteriosclerosis. 1988 Jan-Feb;8(1):46–56. doi: 10.1161/01.atv.8.1.46. [DOI] [PubMed] [Google Scholar]
  27. Slotte J. P., Oram J. F., Bierman E. L. Binding of high density lipoproteins to cell receptors promotes translocation of cholesterol from intracellular membranes to the cell surface. J Biol Chem. 1987 Sep 25;262(27):12904–12907. [PubMed] [Google Scholar]
  28. Steiner A. L., Pagliara A. S., Chase L. R., Kipnis D. M. Radioimmunoassay for cyclic nucleotides. II. Adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in mammalian tissues and body fluids. J Biol Chem. 1972 Feb 25;247(4):1114–1120. [PubMed] [Google Scholar]
  29. VAHOUNY G. V., WEERSING S., TREADWELL C. R. MICELLAR-SOLUBILIZED SUBSTRATES AND CHOLESTEROL ESTERASE ACTIVITY IN VITRO. Arch Biochem Biophys. 1964 Jul;107:7–15. doi: 10.1016/0003-9861(64)90262-0. [DOI] [PubMed] [Google Scholar]
  30. Vane J. R. Prostaglandins and the cardiovascular system. Br Heart J. 1983 May;49(5):405–409. doi: 10.1136/hrt.49.5.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wynalda M. A., Lincoln F. H., Fitzpatrick F. A. High-performance liquid chromatographic assay for prostacyclin. J Chromatogr. 1979 Sep 1;176(3):413–417. doi: 10.1016/s0021-9673(00)89460-1. [DOI] [PubMed] [Google Scholar]
  32. Yui Y., Aoyama T., Morishita H., Takahashi M., Takatsu Y., Kawai C. Serum prostacyclin stabilizing factor is identical to apolipoprotein A-I (Apo A-I). A novel function of Apo A-I. J Clin Invest. 1988 Sep;82(3):803–807. doi: 10.1172/JCI113682. [DOI] [PMC free article] [PubMed] [Google Scholar]

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