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Insight into the Role of LCAT from Mouse Models

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References

  1. Glomset JA. The mechanism of the plasma cholesterol esterification reaction: Plasma fatty acid transferase.Biochim Biophys Acta1962, 65:128–135.

    Google Scholar 

  2. Lacko AG, Pritchard PH. International Symposium on Reverse Cholesterol Transport. Report on a meeting. J Lipid Res1990, 31:2295–2299.

    Google Scholar 

  3. Rader DJ. Regulation of reverse cholesterol transport and clinical implications. Am J Cardiol2003 92(4A):42J–49J.

    Google Scholar 

  4. Knight BL. ATP-binding cassette transporter A1: Regulation of cholesterol efflux. Biochem Soc Trans2004 32(Pt 1):124–127.

    Google Scholar 

  5. Zhang Y, Zanotti I, Reilly MP, Glick JM, Rothblat GH, Rader DJ. Overexpression of apolipoprotein A-I promotes reverse transport of cholesterol from macrophages to feces in vivo. Circulation2003 108:661–663.

    Google Scholar 

  6. Rader DJ, Ikewaki K, Duverger N, Schmidt H, Pritchard H, Frohlich J, Clerc M, Dumon MF, Fairwell T, Zech L. Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease. J Clin Invest1994 93:321–330.

    Google Scholar 

  7. Kuivenhoven JA, Pritchard H, Hill J, Frohlich J, Assmann G, Kastelein J. The molecular pathology of lecithin: cholesterol acyltransferase( LCAT) deficiency syndromes. J Lipid Res1997 38:191–205.

    Google Scholar 

  8. Borysiewicz LK, Soutar AK, Evans DJ, Thompson GR, Rees AJ. Renal failure in familial lecithin: cholesterol acyltransferase defi-ciency. Q J Med1989 51:411–426.

    Google Scholar 

  9. Santamarina-Fojo S, Lambert G, Hoeg JM, Brewer HB Jr. Lecithincholesterol acyltransferase: role in lipoprotein metabolism, reverse cholesterol transport and atherosclerosis. Curr Opin Lipidol2000 11:267–275.

    Google Scholar 

  10. Francone OL, Gong EL, Ng DS, Fielding CJ, Rubin EM. Expression of human lecithincholesterol acyltransferase in transgenic LCAT in Metabolism, and Atherosclerosismice. Effect of human apolipoprotein AI and human apolipoprotein all on plasma lipoprotein cholesterol metabolism. J Clin Invest1995 96:1440–1448.

    Google Scholar 

  11. Mehlum A, Gjernes E, Solberg LA, Hagve TA, Prydz H. Overexpression of human lecithin: cholesterol acyltransferase in mice offers no protection against diet-induced atherosclerosis. APMIS2000 108:336–342.

    Google Scholar 

  12. Furbee JW Jr, Parks JS. Transgenic overexpression of human lecithin: cholesterol acyltransferase (LCAT) in mice does not increase aortic cholesterol deposition. Atherosclerosis2002 165:89–100.

    Google Scholar 

  13. Vaisman BL, Klein HG, Rouis M, Berard AM, Kindt MR, Talley GD, Meyn SM, Hoyt RF Jr, Marcovina SM, Albers JJ, Hoeg JM, Brewer B Jr, Santamarina-Fojo S. Overexpression of human lecithin cholesterol acyltransferase leads to hyperalphalipoproteinemia in transgenic mice. J Biol Chem1995 270:12269-12275.

    Google Scholar 

  14. Berard AM, Foger B, Remaley A, Shamburek R, Vaisman BL, Talley G, Paigen B, Hoyt RF Jr, Marcovina S, Brewer HB Jr, Santamarina-Fojo S. High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase. Nat Med1997 3:744–749.

    Google Scholar 

  15. Foger B, Chase M, Amar MJ, Vaisman BL, Shamburek RD, Paigen B, Fruchart-Najib J, Paiz JA, Koch CA, Hoyt RF, Brewer HB Jr, Santamarina-Fojo S. Cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin cholesterol acyltransferase transgenic mice. J Biol Chem1999 274:36912–36920.

    Google Scholar 

  16. Mertens A, Verhamme P, Bielicki JK, Phillips MC, Quarck R, Verreth W, Stengel D, Ninio E, Navab M, Mackness B, Mackness M, Holvoet P. Increased low-density lipoprotein oxidation and impaired high-density lipoprotein antioxidant defense are associated with increased macrophage homing and atherosclerosis in dyslipidemic obese mice: LCAT gene transfer decreases atherosclerosis. Circulation2003 107:1640–1646.

    Google Scholar 

  17. Ng DS, Francone OL, Forte TM, Zhang J, Haghpassand M, Rubin EM. Disruption of the murine lecithin: cholesterol acyltransferase gene causes impairment of adrenal lipid delivery and up-regulation of scavenger receptor class B type I. J Biol Chem1997 272:15777–15781.

    Google Scholar 

  18. Sakai N, Vaisman BL, Koch CA, Hoyt RF Jr, Meyn SM, Talley GD, Paiz JA, Brewer HB Jr, Santamarina-Fojo S. Targeted disruption of the mouse lecithin: cholesterol acyltransferase (LCAT) gene. Generation of a new animal model for human LCAT deficiency. J Biol Chem1997 272:7506–7510.

    Google Scholar 

  19. Forte T, Nichols A, Glomset J, Norum K.The ultrastructure of plasma lipoproteins in lecithin: cholesterol acyltransferase defi-ciency. Scand J Clin Lab Invest Suppl1974 137:121–132.

    Google Scholar 

  20. Lambert G, Sakai N, Vaisman BL, Nevfeld EB, Marteyn B, Chan C-C, Paigen B, Lupia E, Thomas A, Striker LJ, Blanchette-Mackie J, Csako G, Brady JN, Costello R, Striker GE, Remaley AT, Brewer B Jr, Santamarina-Fojo S. Analysis of glomerulosclerosis and atherosclerosis in lecithin cholesterol acyltransferase-deficient mice. J Biol Chem2001 276:15090–15098.

    Google Scholar 

  21. Furbee JW Jr, Sawyer JK, Parks JS. Lecithin: cholesterol acyltransferase deficiency increases atherosclerosis in the low density lipoprotein receptor and apolipoprotein E knockout mice. J Biol Chem2002 277:3511–3519.

    Google Scholar 

  22. Ng DS, Maguire GF, Wylie J, Ravandi A, Xuan W, Ahmed Z, Eskandarian M, Kuksis A, Connelly PW. Oxidative stress is markedly elevated in lecithin: cholesterol acyltransferasedeficient mice and is paradoxically reversed in the apolipoprotein E knockout background in association with a reduction in atherosclerosis. J Biol Chem2002 277:11715–11720.

    Google Scholar 

  23. Forte TM, Oda MN, Knoff L, Frei B, Suh J, Harmony JA, Stuart WD, Rubin EM, Ng DS. Targeted disruption of the murine lecithin: cholesterol acyltransferase gene is associated with reductions in plasma paraoxonase and platelet-activating factor acetylhydrolase activities but not in apolipoprotein J concentration. J Lipid Res1999 40:1276–1283.

    Google Scholar 

  24. Sorenson RC, Bisgaier CL, Aviram M, Hsu C, Billecke S, La Du BN. Human serum Paraoxonase/Arylesterase's retained hydrophobic N-terminal leader sequence associates with HDLs by binding phospholipids: apolipoprotein A-I stabilizes activity. Arterioscler Thromb Vasc Biol1999 19:2214–2225.

    Google Scholar 

  25. Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature1998 394:284–287.

    Google Scholar 

  26. Tward A, Xia YR, Wang XP, Shi YS, Park C, Castellani LW, Lusis AJ, Shih DM. Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation2002 106:484–490.

    Google Scholar 

  27. Rozenberg O, Rosenblat M, Coleman R, Shih DM, Aviram M. Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: Studies in PON1-knockout mice. Free Radic Biol Med2003 34:774–784.

    Google Scholar 

  28. Furbee JW Jr, Francone O, Parks JS. in vivocontribution of LCAT to apolipoprotein B lipoprotein cholesteryl esters in LDL receptor and apolipoprotein E knockout mice. J Lipid Res2002 43:428–437.

    Google Scholar 

  29. Zhao Y, Thorngate FE, Weisgraber KH, Williams DL, Parks JS. Apolipoprotein E is the major physiological activator of lecithincholesterol acyltransferase on apolipoproteins B lipoprotein particles. Arteriosclerol Thromb Vasc Biol2004 P461.

  30. Brunzell JD, Ayyobi AF. Dyslipidemia in the metabolic syndrome and type 2 diabetes mellitus. Am J Med2003 115(Suppl 8A):24S–28S.

    Google Scholar 

  31. Kodama T, Akanuma Y, Okazaki M, Aburatani H, Itakura H, Takahashi K, Sakuma M, Takaku F, Hara I. Abnormalities in plasma lipoprotein in familial partial lecithin: cholesterol acyltransferase deficiency. Biochim Biophys Acta1983 752:407–415.

    Google Scholar 

  32. Frohlich J, McLeod R, Pritchard PH, Fesmire J, McConathy W. Plasma lipoprotein abnormalities in heterozygotes for familial lecithin: cholesterol acyltransferase deficiency. Metabolism1988 37:3–8.

    Google Scholar 

  33. Hoeg JM, Vaisman BL, Demosky SJ Jr, Meyn SM, Talley GD, Hoyt RF Jr, Feldman S, Berard AM, Sakai N, Wood D, Brousseau ME, Marcovina S, Brewer HB Jr, Santamarina-Fojo S. Lecithin: cholesterol acyltransferase overexpression generates hyperalphalipoproteinemia and a nonatherogenic lipoprotein pattern in transgenic rabbits. J Biol Chem1996 271:4396–4402.

    Google Scholar 

  34. Blomhoff JP, Holme R, Sauar J, Gjone E. Familial lecithin: cholesterol acyltransferase deficiency. Further studies on plasma lipoproteins and plasma postheparin lipase activity of a patient with normal renal function. Scand J Clin Lab Invest Suppl1978 150:177–182.

    Google Scholar 

  35. Ng DS, Xie C, Maguire GF, Zhu X, Ugwu F, Lam E, Connelly PW. Hypertriglyceridemia in lecithin-cholesterol acyltransferasedeficient mice is associated with hepatic overproduction of triglycerides, increased lipogenesis, and improved glucose tolerance. J Biol Chem2004 279:7636–7642.

    Google Scholar 

  36. Cao G, Liang Y, Broderick CL, Oldham BA, Beyer TP, Schmidt RJ, Zhang Y, Stayrook KR, Suen C, Otto KA, Miller AR, Dai J, Foxworthy P, Gao H, Ryan TP, Jiang XC, Burris TP, Eacho PI, Etgen GJ. Antidiabetic action of a liver x receptor agonist mediated by inhibition of hepatic gluconeogenesis. J Biol Chem2003 278:1131–1136.

    Google Scholar 

  37. Pawar A, Botolin D, Mangelsdorf DJ, Jump DB. The role of liver X receptor-alpha in the fatty acid regulation of hepatic gene expression. J Biol Chem2003 278:40736–40743.

    Google Scholar 

  38. Sekiya M, Yahagi N, Matsuzaka T, Najima Y, Nakakuki M, Nagai R, Ishibashi S, Osuga J, Yamada N, Shimano H. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology2003 38:1529–1539.

    Google Scholar 

  39. Field FJ, Born E, Murthy S, Mathur SN. Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: Effect on fatty acid synthesis and triacylglycerol transport. Biochem J2002 368:855–864.

    Google Scholar 

  40. Santamarina-Fojo S, Hoeg JM, Assmann G, Bryan Brewer H Jr. Lecithin cholesterol acyltransferase deficiency and fish eye disease. In: Scriver CR, Beaudet AL, Sly WS, et al. The Metabolic and Molecular Bases of Inherited Disease(8th ed.).NewYork: McGraw-Hill, 2001:2817–2833.

    Google Scholar 

  41. Lynn EG, Siow YL, Frohlich J, Cheung GT, O K. Lipoprotein-X stimulates monocyte chemoattractant protein-1 expression in mesangial cells via nuclear factor-kappa B. Kidney Int2001 60:520–532.

    Google Scholar 

  42. Zhu X, Herzenberg AM, Eskandrian M, Maguire GF, Scholey JW, Connelly PW, Ng DS. A novel in vivolecithin-cholesterol acyltransferase (LCAT) deficient mouse expressing predominantly LpX is associated with spontaneous glomerulopathy. Am J Path2004in press.

  43. Massey AR, Miao L, Smith BN, Liu J, Kusaka I, Zhang JH, Tang J. Increased RhoA translocation in renal cortex of diabetic rats. Life Sci2003 72:2943–2952.

    Google Scholar 

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Ng, D.S. Insight into the Role of LCAT from Mouse Models. Rev Endocr Metab Disord 5, 311–318 (2004). https://doi.org/10.1023/B:REMD.0000045102.70521.af

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