Journal Articles

LCAT Deficiency Syndromes

Duivenvoorden R, Holleboom AG, van den Bogaard B, Nederveen AJ, de Groot E, Hutten BA, Schimmel AW, Hovingh GK, Kastelein JJP, Kuivenhoven JA, Stroes ESG.  Carriers of lecithin cholesterol acyltransferase gene mutations have accelerated atherogenesis as assessed by carotid 3.0-T magnetic resonance imaging.  J Am Coll Cardiol 2011;58:2481-2487.http://www.ncbi.nlm.nih.gov/pubmed/22133847

Holleboom AG, Kuivenhoven JA, Peelman F, Schimmel AW, Peter J, Defesche JC, Kastelein JJP, Hovingh GV, Stroes ES, Motazacker MM.  High prevalence of mutations in LCAT in patients with low HDL cholesterol levels in The Netherlands:  identification and characterization of eight novel mutations.  Human Mutation 2011; 32:1290-1298.  http://www.ncbi.nlm.nih.gov/pubmed/21901787

Holleboom AG, Kuivenhoven JA, van Olden CC, Peter J, Schimmel AW, Levels JH, Valentijn RM, Vos P, Defesche JC, Kastelein JJP, Hovingh GK, Stroes ESG, Hollak CEM.  Proteinuria in early childhood due to familial LCAT deficiency caused by loss of a disulfide bond in lecithin:cholesterol acyltransferase.  Atherosclerosis 2011;216:161-165.http://www.ncbi.nlm.nih.gov/pubmed/21315357

Hovingh GK, Hutten BA, Holleboom AG, Petersen W, Rol P, Stalenhoef A, Zwinderman AH, de GE, Kastelein JJ, Kuivenhoven JA. Compromised LCAT function is associated with increased atherosclerosis. Circulation 2005;112:879-884. http://www.ncbi.nlm.nih.gov/pubmed/16061733

Kiss RS, Kavaslar N, Okuhira K, Freeman MW, Walter S, Milne RW, McPherson R, Marcel YL.  Genetic etiology of isolated low HDL syndrome.  Incidence and heterogeneity of efflux defects.  Arterioscler Thromb Vasc Biol 27:1139-1145, 2007. http://www.ncbi.nlm.nih.gov/pubmed/17303779

Kuivenhoven JA, Pritchard H, Hill J, Frohlich J, Assmann G, Kastelein J. The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes. J Lipid Res 1997;38:191-205.
http://www.ncbi.nlm.nih.gov/pubmed/9162740

Miettinen HE, Gylling H, Tenhunen J, Virtamo J, Jauhiainen M, Huttunen JK, Kantola I, Miettinen TA, Kontula K.  Molecular genetic study of Finns with hypoalphalipoproteinemia and hyperalphalipoproteinemia.  A novel Gly230Arg muation (LCATFin) of lecithin:cholesterol acyltransferase (LCAT) accounts for 5% of cases with very low serum HDL cholesterol levels.  Arterioscler Thromb Vasc Bioil 18:591-598, 1998. http://www.ncbi.nlm.nih.gov/pubmed/9555865

Murayama N,  Asano Y, Hosoda S, Maesawa M, Saito M, Takaku F, Sugihara T, Miyashima Y, Yawata Y. Decreased sodium influx and abnormal red cell membrane lipids in a patient with familial plasma lecithin: cholesterol acyltransferase deficiency.  Am J Hematol 1984;16:129-137. http://www.ncbi.nlm.nih.gov/pubmed/6695915

Recalde D, Cenarro A, Garcia-Otin A-L, Gomez-Coronado D, Civeira F, Pocovi M.  Analysis of apoA-I, lecithin:cholesterol acyltransferase and glucocerebrosidase genes in hypoalphalipoproteinemia. Atherosclerosis 163:49-58, 2002. http://www.ncbi.nlm.nih.gov/pubmed/12048121

Roshan B, Ganda OP, Desilva R, Ganim RB, Ward E, Haessler SD, Polisecki EY, Asztalos BF, Schaefer EJ.  Homozygous lecithin:cholesterol acyltransferase (LCAT) deficiency due to a new loss of function mutation and review of the literature.  J Clin Lipidol 2011;5:493-499.  http://www.ncbi.nlm.nih.gov/pubmed/22108153

Rousset X, Vaisman B, Auerbach B, Krause BR, Homan R, Stonik J, Csako G, Shamburek R, Remaley AT. Effect of recombinant human lecithin-cholesterol:acyltransferase infusion on lipoprotein metabolism in mice. J Pharm Exptl Therap. 2010a;335:140-148. http://www.ncbi.nlm.nih.gov/pubmed/20605907

Rousset X, Vaisman B, Krause B, Homan R, Auerbach B, Remaley A.  Recombinant lecithin:cholesterol acyltransferase (rLCAT): investigation of its use as an enzyme replacement therapy for LCAT deficiency and atherosclerosis.  6th IAS-Sponsored Workshop on High Density Lipoproteins, Whistler, British Columbia, May 17-20, 2010b, p. 73 (abstract/poster).

Santamarina-Fojo S, Hoeg JM, Assmann G, Brewer HB. Lecithin Cholesterol Acyltransferase Deficiency and Fish Eye Disease. In:  Metabolic & Molecular Bases of Inherited Disease. Scriver CR, beaudet D, Valle D, Sly W, Childs B, Kinzler K et al., eds. Eighth ed. New York: McGraw-Hill; 2006, p. 2817-2833.

van den Bogaard B, Holleboom AG, Duivenvoorden R, Hutten BA, Kastelein JJP, Hovingh GK, Kuivenhoven JA, Stroes ESG, van den Born B-JH.  Patients with low HDL-cholesterol caused by mutations in LCAT have increased arterial stiffness.  Atherosclerosis, Sept 27, 2012.  Epub ahead of press.  http://www.ncbi.nlm.nih.gov/pubmed/23078883

Zhu X, Herzenberg AM, Eskandarian M, Maguire GF, Scholey JW, Connelly PW, Ng DS.  A novel in vivo lecithin-cholesterol acyltransferase (LCAT)-deficient mouse expressing predominantly LpX is associated with spontaneous glomerulopathy.  Am J Path 2004;165:1269-1278. http://www.ncbi.nlm.nih.gov/pubmed/15466392

 

Atherosclerosis

Amar MJ, Shamburek RD, Vaisman B, Knapper CL, Foger B, Hoyt RF, Jr., Santamarina-Fojo S, Brewer HB, Jr., Remaley AT. Adenoviral expression of human lecithin-cholesterol acyltransferase in nonhuman primates leads to an antiatherogenic lipoprotein phenotype by increasing high-density lipoprotein and lowering low-density lipoprotein. Metabolism 2009;58:568-575.
http://www.ncbi.nlm.nih.gov/pubmed/19303980

Asztalos BF, Roheim PS, Milani RL, Lefevre M, McNamara JR, Horvath KV, Schaefer EJ. Distribution of ApoA-I-containing HDL subpopulations in patients with coronary heart disease. Arterioscler Thromb Vasc Biol 2000;20:2670-2676.
http://www.ncbi.nlm.nih.gov/pubmed/11116070

Asztalos BF, Collins D, Cupples LA, Demissie S, Horvath KV, Bloomfield HE, Robins SJ, Schaefer EJ.  Value of high-density lipoprotein (HDL) subpopulations in predicting recurrent cardiovascular events in the Veterans Affairs HDL Intervention Trial.  Arterioscler Thromb Vasc Biol 2005;25:2185-2191. http://www.ncbi.nlm.nih.gov/pubmed/16123324

Chen Z, Ichetovkin M, Kurtz M, Zycband E, Kawka D, Woods J, He X, Plump AS, Hailman E.  Cholesterol in human atherosclerotic plaque is a marker for underlying disease state and plaque vulnerability.  Lipids in Health and Disease 2010;9:61-68. http://www.ncbi.nlm.nih.gov/pubmed?term=Chen%20Z%20and%20Plump

Chen Z, Chu D, Castro-Perez JM, Ni W, Zhang A, Krsmanovic ML, Xie D, Shah V, Stout SJ, McLaren DG, Stefanni AC, Lee SH, Roddy TP, Plump AS, Hubbard BK, Vogt TF, Zhou HH.  AAV8-mediated long-term expression of human LCAT significantly improves lipid profiles in hCETP;Ldlr +/- mice.  J Cardovasc Trans Res 2011;4:801-810. http://www.ncbi.nlm.nih.gov/pubmed/21822774

Chen Z, Wang S-P, Krsmanovic ML, Castro-Perez J, Gagan K, Mendoza V, Rosa R, Shah V, He T, Stout SJ, Geoghagen NS, Lee SH, McLaren DF, Wang L, Roddy TP, Plump AS, Hubbard BK, Sinz CJ, Johns DG.  Small molecule activation of lecithin cholesterol acyltransferase modulates lipoprotein metabolism in mice and hamsters.  Metabolism 2011;Oct 14 [Epub ahead of print].  http://www.ncbi.nlm.nih.gov/pubmed/22001333

Guey LT, Pullinger CR, Ishida BY, O’Connor PM, Zellner C, Francone OL, Laramie JM, Naya-Vigne JM, Siradze KA, Deedwania P, Redberg RF, Frost PH, Seymour AB, Kane JP, Malloy MJ.  Relation of increased prebeta-1 high-density lipoprotein levels to risk of coronary heart disease.  Am J Cardiol 2011;108:360-366. http://www.ncbi.nlm.nih.gov/pubmed/21757044

Hoeg JM, Santamarina-Fojo S, Bérard AM, Cornhill JF, Herderick EE, Feldman SH, Haudenschild CC, Vaisman BL, Hoyt RF, Jr., Demosky SJ, Jr., Kauffman RD, Hazel CM, Marcovina SM, Brewer HB, Jr. Overexpression of lecithin:cholesterol acyltransferase in transgenic rabbits prevents diet induced atherosclerosis. Proc Natl Acad Sci USA 1996;93:11448-53. http://www.ncbi.nlm.nih.gov/pubmed/8876155

Hoeg JM, Vaisman BL, Demosky SJ, Jr., Meyn SM, Talley GD, Hoyt RF, Jr., Feldman S, Bérard AM, Sakai N, Wood D, Brousseau ME, Marcovina S, Brewer HB, Jr., Santamarina-Fojo S.Lecithin:cholesterol acyltransferase overexpression generates
hyperalpha-lipoproteinemia and a nonatherogenic lipoprotein pattern in transgenic rabbits. J Biol
Chem 1996;271:4396-402. http://www.ncbi.nlm.nih.gov/pubmed/8626790

Kane JP, Malloy MJ.  Prebeta-1 HDL and coronary heart disease.  Curr Opin Lipidol 23:367-371, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22517613

Kunnen S, Van Eck M.  Lecithin:cholesterol acyltransferase: old friend or foe in atherosclerosis?  J Lipid Res 53:1783-1799, 2012. http://www.ncbi.nlm.nih.gov/pubmed?term=Kunnen%20and%20van%20Eck

Lamon-Fava S, Herrington DM, Reboussin DM, Sherman M, Horvath KV, Cupples LA, White C, Demissie S, Schaefer EJ, Asztalos BF.  Plasma levels of HDL subpopulations and remnant lipoproteins predict the extent of angiographically-defined coronary heart disease in postmenopausal women.  Arterioscler Thromb Vasc Biol 2008;28:575-579. http://www.ncbi.nlm.nih.gov/pubmed/18174456

Miida T, Nakamura Y, Inano K, Matsuto T, Yamaguchi T, Tsuda T, Okada M.  Pre beta 1-high-density lipoprotein increases in coronary artery disease. Clin Chem 1996;42:1992-1995. http://www.ncbi.nlm.nih.gov/pubmed/8969638

Nakamura Y, Kotite L, Gan Y, Spencer TA, Fielding CJ, Fielding PE. Molecular mechanism of reverse cholesterol transport:  reaction of pre-β-migrating high-density lipoprotein with plasma lecithin/cholesterol acyltransferase.  Biochemistry 2004;43:14811-14820. http://www.ncbi.nlm.nih.gov/pubmed/15544352

Sethi AA, Sampson M, Warnick R, Muniz N, Vaisman B, Nordestgaard BG, Tybjaerg-Hansen A, Remaley AT.  High pre-beta HDL concentrations and low lecithin:cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol.  Clin Chem 56:1128-1137. http://www.ncbi.nlm.nih.gov/pubmed/20511449

Solajic-Bozicevic N, Stavljenic-Rukavina A, Sesto M. Lecithin-cholesterol acyltransferase activity in patients with coronary artery disease examined by coronary angiography. Clin Investig 1994;72:951-956. http://www.ncbi.nlm.nih.gov/pubmed/7711425

Tashiro J, Miyazaki O, Nakamura Y, Miyazaki A, Fukamachi I, Bujo H, Saito Y. Plasma prebeta1-HDL level is elevated in unstable angina pectoris. Atherosclerosis 2009;204:595-600. http://www.ncbi.nlm.nih.gov/pubmed/19054517

Van Craeyveld E., Lievens J, Jacobs F, Feng Y, Snoeys J, De Geest B. Apolipoprotein A-I and lecithin:cholesterol acyltransferase transfer induce cholesterol unloading in complex atherosclerotic lesions. Gene Ther 2009;16:757-765.  http://www.ncbi.nlm.nih.gov/pubmed/19242527

Zhang AH, Gao S, Fan JL, Huang W, Zhao TQ, Liu G. Increased plasma HDL cholesterol levels and biliary cholesterol excretion in hamster by LCAT overexpression. FEBS Lett 2004;570:25-9. http://www.ncbi.nlm.nih.gov/pubmed/15251433

 

Additional Reading

Auerbach BJ and Parks JS.  (1989) Lipoprotein abnormalities associated with lipopolysaccharide-induced lecithin: cholesterol acyltransferase and lipase deficiency.  J Biol Chem 1989;264:10264-10270. http://www.ncbi.nlm.nih.gov/pubmed/2722868

Feister HA, Auerbach BJ, Cole LA, Krause BR and Karathanasis SK. Identification of an IL-6 response element in the human LCAT promoter.  J Lipid Res 2002;43:960-970.
http://www.ncbi.nlm.nih.gov/pubmed?term=Feister%20HA%20and%20Auerbach

Krause BR, Homan R, Newton R.  High-density lipoprotein and atheroprotection. In: Endothelial Dysfunctions and Vascular Disease.  De Caterina and Libby, eds.  Blackwell Publishing, 2007, p. 95-107.

Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL, Halpern S, Crowe T, Blankenship JC, Kerensky R. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 2003;290:2292-2300. http://www.ncbi.nlm.nih.gov/pubmed/14600188

Rousset X, Vaisman B, Amar M, Sethi AA, Remaley AT. Lecithin: cholesterol acyltransferase—from biochemistry to role in cardiovascular disease. Curr Opin Endocrinol Diabetes Obes 2009;16:163-171. http://www.ncbi.nlm.nih.gov/pubmed/19306528

Rousset X, Shamburek R, Vaisman B, Amar M, Remaley AT.  Lecithin cholesterol acyltransferase:  an anti-or pro-atherogenic factor?   Curr Atheroscler Rep  Feb 18, 2011, Epub ahead of print. http://www.ncbi.nlm.nih.gov/pubmed/21331766

Rye KA, Bursill CA, Lambert G, Tabet F, Barter PJ. The metabolism and anti-atherogenic properties of HDL.  J Lipid Res 2009;50(Supplement):S195-S200. http://www.ncbi.nlm.nih.gov/pubmed/19033213

Shaw JA, Bobik A, Murphy A, Kanellakis P, Blombery P, Mukhamedova N, Woollard K, Lyon S,Sviridov D, Dart AM.  Infusion of reconstituted high-density lipoprotein leads to acute changes inhuman atherosclerotic plaque. Circ Res 2008;103:1084-1091. http://www.ncbi.nlm.nih.gov/pubmed?term=Shaw%20JA%20and%20Bobik

Tardif JC, Gregoire J, L’Allier PL, Ibrahim R, Lesperance J, Heinonen TM, Kouz S, Berry C, Basser R, Lavoie MA, Guertin MC, Rodes-Cabau J. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 2007;297:1675-1682. http://www.ncbi.nlm.nih.gov/pubmed/17387133

Williams KJ, Feig JE, Fisher EA. Cellular and molecular mechanisms for rapid regression of atherosclerosis: from bench top to potentially achievable clinical goal. Curr Opin Lipidol 2007;18:443-450.
http://www.ncbi.nlm.nih.gov/pubmed/17620862

Williams KJ, Feig JE, Fisher EA. Rapid regression of atherosclerosis: insights from the clinical and experimental literature. Nat Clin Pract Cardiovasc Med 2008;5:91-102. http://www.ncbi.nlm.nih.gov/pubmed/18223541

Williams KJ, Tabas I. Lipoprotein retention–and clues for atheroma regression.  Arterioscler Thromb Vasc Biol 2005;25:1536-1540. http://www.ncbi.nlm.nih.gov/pubmed/16055756

 

Presentations at Scientific Meetings

Amar MJ, Vaisman B, Pryor M, Stonik J, Remaley A.  Human LCAT leads to enhanced atheroprotection compared to murine LCAT in apoe knockout mice. Arterioscler Thromb Vasc Biol  Conference, April 28-30, 2011.  Poster P429.

Chen Z, Chu D, Castro-Perez J, Zhang A, Krsmanovic ML, Xie D, Shah V, Stout SJ, McLaren DG, Stefanni AC, Lee SH, Plump AS, Vogt TF, Hubbard BK, Zhou HH.   Profound changes in circulating lipids in hCETP;Ldlr+/- mouse following chronic AAV8-mediated expression of human LCAT.  Arterioscler Thromb Vasc Biol  Conference, April 28-30, 2011.  Poster P361.

Duivenvoorden R, Holleboom AG, van den Bogaard B, de Groot E, Nederveen AJ, Lameris JS, Kastelein JJP, Kuivenhoven JA, Stroes ESG.  Carriers of LCAT gene mutations exhibit increased atherosclerosis: a 3.0 Tesla MRI study.  J Am Coll Cardiol, March 9, 2010.  Volume 55, Issue 10A.

Holleboom AG, Duivenvoorden R, van den Bogaard, de Groot E, Nederveen AJ, Lameris JS, Hutten BA, Kastelein JJ, Kuivenhoven JA.  Patients with low plasma high density lipoprotein-cholesterol due to mutations in the gene encoding for lecithin:cholesterol acyl transferase have increased atherosclerosis:  a 3.0 Tesla MRI study.  Circulation 2010;122:A17773.

Homan R, Esmaeil N, Mendelsohn L, Auerbach B, Krause B, Kato GJ.  Abnormal lipid content of plasma and red blood cells in sickle cell disease is coincident with decreased lecithin:cholesterol acyltransferase in plasma.  Annual National Sickle Cell Disease Scientific Meeting, Hollywood, FL.  March 2, 2012.

Remaley AT.  LCAT therapy for raising HDL.  American Heart Association Scientific Sessions, Orlando, FL.  November, 2011.

Remaley AT.  Recombinant LCAT:  New Potential Therapy for Cardiovascular Disease and Familial LCAT Deficiency.  80th European Atherosclerosis Society Congress Satellite Symposium, High Density Lipoproteins: From Basic Science to Therapeutic Advances.  Milan, Italy.  May 28-29, 2012.

Rousset X, Vaisman B, Krause B, Homan R, Auerbach B, Remaley AT.  Recombinant lecithin:cholesterol acyl transferase (rLCAT):  Investigation of its use as an enzyme replacement therapy for LCAT deficiency and atherosclerosis.  6th IAS-Sponsored Workshop on High Density Lipoproteins, May 17-20, 2010.  Whistler, British Columbia, Canada.  Poster 095, p. 73.

Rousset X, Vaisman B, Stonik J, Duarte CJ, Remaley AT.  Effect of rapid infusion of LCAT on HDL metabolism and its possible utility for enzyme replacement therapy.  XV International Symposium on Atherosclerosis, June 14-18, 2009.  Boston, MA  USA.   Abstract 1465.

Zhou M, Sawyer J, Kelley K, Fordstrom P, Chan J, Tonn G, Carlson T, Retter M, Meininger D, Cheng J, Gates A, Woodward A, Delaney J, Zhang R, Tang J, Liu Q, Cao P, Luchoomun J, Voogt J, Turner S, Shan B, Boone T, Rudel L, Schwarz M.  Lecithin Cholesterol Acyltransferase Promotes Reverse Cholesterol Transport and Attenuates Atherosclerosis Progression in New Zealand White Rabbits. Circulation 2009;120:S1175-S117b.