Recombinant human LCAT normalizes plasma lipoprotein profile in LCAT deficiency.

Abstract

Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. Mutations in the LCAT gene leads to two rare disorders, familial LCAT deficiency and fish-eye disease, both characterized by severe hypoalphalipoproteinemia associated with several lipoprotein abnormalities. No specific treatment is presently available for genetic LCAT deficiency. In the present study, recombinant human LCAT was expressed and tested for its ability to correct the lipoprotein profile in LCAT deficient plasma. The results show that rhLCAT efficiently reduces the amount of unesterified cholesterol (-30%) and promotes the production of plasma cholesteryl esters (+210%) in LCAT deficient plasma. rhLCAT induces a marked increase in HDL-C levels (+89%) and induces the maturation of small preβ-HDL into alpha-migrating particles. Moreover, the abnormal phospholipid-rich particles migrating in the LDL region were converted in normally sized LDL.

• Authors: Sara Simonelli, Cristina Tinti, Laura Salvini, Laura Tinti, Alice Ossoli, Cecilia Vitali, Vitor Sousa, Gaetano Orsini, Maria Luisa Nolli, Guido Franceschini, Laura Calabresi
• Journal: Biologicals : journal of the International Association of Biological Standardization (Biologicals) Vol. 41 Issue 6 Pg. 446-9 (Nov 2013) ISSN: 1095-8320 [Electronic] England
• PMID: 24140107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Lipoproteins
• Recombinant Proteins
• Cholesterol
• Phosphatidylcholine-Sterol O-Acyltransferase

Topics

• Blotting, Western
• Cholesterol (blood, metabolism)
• Family Health
• HEK293 Cells
• Humans
• Lecithin Cholesterol Acyltransferase Deficiency (blood, genetics)
• Lipoproteins (blood, metabolism)
• Mutation
• Phosphatidylcholine-Sterol O-Acyltransferase (blood, genetics, metabolism)
• Recombinant Proteins (blood, metabolism)