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Effect of trifluoperazine on certain arterial wall lipid-metabolizing enzymes inducing atherosclerosis in rhesus monkeys

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Lipids

Abstract

The effect of trifluoperazine (TFP) was investigated on arterial wall lipid-metabolizing enzymes like acyl-CoA:cholesterol acyltransferase (ACAT) and cholesterol ester hydrolase (CEH) in rhesus monkeys. The activity was determined in aortic wall homogenates obtained from rhesus monkeys fed an atherogenic diet coupled with intramuscular injections of adrenaline and TFP. Although TFP had no significant effect on serum cholesterol and triglycerides, it decreased significantly the formation of atherosclerotic lesions by decreasing the esterification of cholesterol, by inhibiting ACAT and enhancing its utilization by activating CEH. Hence, the preventive effect of TFP on the development of atherosclerosis in rhesus monkeys is mediated through its ability to influence the activities of arterial wall lipid-metabolizing enzymes like ACAT and CEH.

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Abbreviations

ACAT:

acyl-CoA:cholesterol acyltransferase

CEH:

cholesterol ester hydrolase

TFP:

trifluoperazine

References

  1. Strong, J.P. (1992) Atherosclerotic Lesions: Natural History, Risk Factors, and Topography, Arch. Pathol. Lab. Med. 116, 1268–1275.

    PubMed  CAS  Google Scholar 

  2. Feldman, D.L., Hoff, H.F., and Gerrity, R.G. (1984) Immunohistochemical Localization of Apo B in Aortas from Hyperlipidemic Swine. Preferential Accumulation in Lesion-Prone Areas, Arch. Pathol. Lab. Med. 108, 817–822.

    PubMed  CAS  Google Scholar 

  3. Jokinen, M.P., Clarkson, T.B., and Prichard, R.W. (1985) Animal Models in Atherosclerosis Research, Exp. Mol. Pathol. 42, 1–28.

    Article  PubMed  CAS  Google Scholar 

  4. Edelstein, C., Lin, C.T., and Scanu, A.M. (1973) The Serum High Density Lipoproteins of Macacus rhesus. II. Isolation, Purification, and Characterization of Their Two Major Polypeptides, J. Biol. Chem. 248, 7653–7660.

    PubMed  CAS  Google Scholar 

  5. Woolf, N. (1993) The Atherosclerotic Arterial Wall, Biochem. Soc. Trans. 21(3), 639–642.

    PubMed  CAS  Google Scholar 

  6. Morin, R.J., Zemplenyi, T., and Peng, S.K. (1987) Metabolism of the Arterial Wall—Influence of Atherosclerosis and Drugs, Pharmacol. Ther. 32, 237–283.

    Article  PubMed  CAS  Google Scholar 

  7. Hollander, W., Kramsch, M., and Fanzblan, C. (1974) Suppression of Atheromatous Fibrous Plaque Formation by Antiproliferative and Antiinflammatory Drugs, Circ. Res. 34&35 (Suppl. 1), 131–141.

    Google Scholar 

  8. Pynadath, T.I., and Chanpai, S. (1981) Elevation of Serum HDL and HDL-C in Cholesterol-Fed Male Rabbits with Estrogen. Atherosclerosis 38, 255–265.

    Article  PubMed  CAS  Google Scholar 

  9. Bell, F.P., and Hubert, E.V. (1981) Membrane-Active Agents. Effect of Various Anesthetics and Chlorpromazine on Arterial Lipid Metabolism, Atherosclerosis 39, 517–525.

    Article  PubMed  CAS  Google Scholar 

  10. Orekhov, A.N., Tertov, V.V., Kudryashov, S.A., Khashimov, Kh.A., and Smirnov, V.N. (1986) Primary Culture of Human Aortic Intima Cells as a Model for Testing Anti-Atherosclerotic Drugs. Effects of Cyclic AMP, Prostaglandins, Calcium Antagonists, Antioxidants, and Lipid-Lowering Agents, Atherosclerosis, 60, 101–110.

    Article  PubMed  CAS  Google Scholar 

  11. Grataroli, R., De Caro, A., and Guy, O. (1981) Biochimie 63, 677–684.

    PubMed  CAS  Google Scholar 

  12. Takai, Y., and Kikkawa, V. (1984) in Advances in Cyclic Nucleotide and Protein Phosphorylation Research (Greengard, P., and Robinson, G.A., eds.) Vol. 18 p. 650. Raven Press, New York.

    Google Scholar 

  13. Mohindroo, A., Kukreja, R.S., and Kaul, D. (1989) Preventive Effect of TFP on Atherosclerosis Induced by Cholesterol and Adrenaline in Rabbits, Indian J. Med. Res. 90, 215–219.

    PubMed  CAS  Google Scholar 

  14. Bocan, T.M.A., Mueller, S.B., Uhlendorf, P.D., Newton, R.S., and Krause, B.R. (1991) Comparison of CI-976, an ACAT Inhibitor and Selected Lipid-Lowering Agents for Antiatherosclerotic Activity in Iliac-Fermoral and Thoraxic Aortic Lesions, Arterio. Thromb. 11, 1830–1843.

    CAS  Google Scholar 

  15. Ishii, T., Oka, M., Katto, N., Shirai, K., Saito, Y., and Hirose, S. (1992) B-VLDL-Induced Cholesterol Ester Deposition in Macrophages May Be Regulated by Neutral Cholesterol Esterase Activity. Arterio. Thromb. 12, 1139–1145.

    CAS  Google Scholar 

  16. Zak, D. (1957) Simple and Rapid Microtechnique for the Serum Total Cholesterol, Am. J. Clin. Pathol. 27, 583–585.

    PubMed  CAS  Google Scholar 

  17. Gottfried, S.P., and Rosenberg, B. (1973) Improved Manual Spectrophotometric Procedure for Determination of Serum Triglycerides, Clin. Chem. 19, 1077–1080.

    PubMed  CAS  Google Scholar 

  18. Chung, B.H., Wilkinson, T., Geer, J.C., and Segrest, J.P. (1980) Preparative and Quantitative Isolation of Plasma Lipoproteins: Rapid, Single Discontinuous Density Gradient Ultracentrifugation in a Vertical Rotor, J. Lipid Res. 21, 284–290.

    PubMed  CAS  Google Scholar 

  19. Stein, Y., Stein, O., and Shapiro, B. (1963) Enzyme Pathways of Glyceride and Phospholipid Synthesis in Aortic Homogenates, Biochim. Biophys. Acta 70, 33–42.

    Article  PubMed  CAS  Google Scholar 

  20. Balasubramaniam, S., Mitropoulos, K.A., and Venkatesan, S. (1978) Rat Liver Acyl-CoA: Cholesterol Acyltransferase, Eur. J. Biochem. 90, 265–267.

    Article  Google Scholar 

  21. Yao, J.K., and Rastetter, G.M. (1985) Microanalysis of Complex Tissue Lipids by High-Performance Thin-Layer Chromatography, Anal. Biochem. 150, 111–116.

    Article  PubMed  CAS  Google Scholar 

  22. Brecher, P., Kessler, M., Clifford, C., and Chobianian, C.L. (1973) Cholester Ester Hydrolysis in Aortic Tissue, Biochim. Biophys. Acta 316, 386–394.

    PubMed  CAS  Google Scholar 

  23. Kukreja, R.S., Bhardwaj, J.R., Datta, B.N., and Chakravorti, R.N. (1984) Aortic Enzyme Alterations in Experimentally Induced Atherosclerosis in Rhesus Monkeys, Indian J. Med. Res. 79, 260–267.

    PubMed  CAS  Google Scholar 

  24. Massom, L. (1990) TFP Binding to Porcine Brain Calmodulin and Skeletal Muscle Troponin C, Biochemistry 29, 671–681.

    Article  PubMed  CAS  Google Scholar 

  25. Mehta, U., and Kaul, D. (1990) Effect of Trifluoperazine and Colchicine on Smooth Muscle Cellular Proliferative and Secretory Activity Induced by Hypercholesterolemic Medium in vitro, Biochem. Int. 21, 107–116.

    PubMed  CAS  Google Scholar 

  26. Scaffer, S.A., Bloom, J.D., Devries, V.G., Dutia, M., Katocs, A.S., Jr., and Largis, E.E. (1986) CL 277082, a Novel Inhibitor of Cholesterol Esterification and Cholesterol Absorption, in Atherosclerosis VII (Fidge, N.H., and Nestel, P.J., eds.) pp. 633–636, Elsevier Science Publishers B.V., Amsterdam.

    Google Scholar 

  27. Middleton, B., Middleton, A., White, D.A., and Bell, G.D. (1984) Dietary Cyclandalate Decreases Pre-Established Atherosclerosis in Rabbits, Atherosclerosis 171, 171–178.

    Article  Google Scholar 

  28. Bell, F.P., Gammill, R.B., and St. John, L.C. (1992) U-73482: A Novel ACAT Inhibitor That Elevates HDL-Cholesterol, Lowers Plasma Triglyceride and Facilitates Hepatic Cholesterol Mobilization in the Rat, Atherosclerosis 92, 115–122.

    Article  PubMed  CAS  Google Scholar 

  29. Khoo, J.C., Mahaney, E.M., and Steinberg, D. (1981) Neutral Cholesterol Esterase Activity in Macrophages and Its Enhancement by cAMP-Dependent Protein Kinase, J. Biol. Chem. 256, 12659–12661.

    PubMed  CAS  Google Scholar 

  30. Brecher, P., Pyun, H.Y., and Chobanian, A.V. (1977) Effect of Atherosclerosis on Lysosomal Cholesterol Esterase Activity in Rabbit Aorta, J. Lipid. Res. 18, 154–162.

    PubMed  CAS  Google Scholar 

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Mohindroo, A., Ahluwalia, P. Effect of trifluoperazine on certain arterial wall lipid-metabolizing enzymes inducing atherosclerosis in rhesus monkeys. Lipids 32, 867–872 (1997). https://doi.org/10.1007/s11745-997-0111-3

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  • DOI: https://doi.org/10.1007/s11745-997-0111-3

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