Journal of Lipid Research (Aug 2020)

Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings

  • Kaare R. Norum,
  • Alan T. Remaley,
  • Helena E. Miettinen,
  • Erik H. Strøm,
  • Bruno E.P. Balbo,
  • Carlos A.T.L. Sampaio,
  • Ingrid Wiig,
  • Jan Albert Kuivenhoven,
  • Laura Calabresi,
  • John J. Tesmer,
  • Mingyue Zhou,
  • Dominic S. Ng,
  • Bjørn Skeie,
  • Sotirios K. Karathanasis,
  • Kelly A. Manthei,
  • Kjetil Retterstøl

Journal volume & issue
Vol. 61, no. 8
pp. 1142 – 1149

Abstract

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LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.

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