Author:
Reyes-Soffer Gissette,Matveyenko Anastasiya,Lignos James,Matienzo Nelsa,Baez Leinys S Santos,Hernandez-One Antonio,Yung Lau,Nandakumar Renu,Singh Sasha A.,Ramakrishnan Rajasekhar,Aikawa Masanori,George Richard,Ginsberg Henry N.
Abstract
AbstractLecithin cholesterol acyl transferase (LCAT) catalyzes the conversion of unesterified, or free cholesterol (FC), to cholesteryl ester (CE), which moves from the surface of HDL into the neutral lipid core. As this iterative process continues, nascent lipid-poor HDL is converted to a series of larger, spherical cholesterol ester enriched HDL particles that can be cleared by the liver in a process that has been termed reverse cholesterol transport (RCT). We conducted a randomized, placebo controlled, cross-over study in 5 volunteers with ASCVD, to examine the effects of an acute increase of recombinant human (rh) LCAT via intravenous administration on the in vivo metabolism of HDL apolipoprotein (APO)A1 and APOA2, and the APOB100-lipoproteins, very low density (VLDL), intermediate density (IDL), and low density (LDL) lipoproteins. As expected, rhLCAT treatment significantly increased HDL CE content. This change did not affect the fractional clearance or production rates of HDL-APOA1 and HDL-APOA2. The metabolism of APOB100-lipoproteins was likewise unaffected. Our results suggest that an acute increase in LCAT activity drives greater flux of CE through the RCT pathway without altering the clearance and production of the main HDL proteins and without affecting the metabolism of APOB100-lipoproteins. Long-term elevations of LCAT might, therefore, have beneficial effects on total body cholesterol balance and atherogenesis.
Publisher
Cold Spring Harbor Laboratory
Reference46 articles.
1. Santamarina-Fojo S , Hoeg JM , Assman G and HB B . Lecithin Cholesterol Acyltransferase Deficiency and Fish Eye Disease. Metabolic and Molecular Bases of Disease. 2006.
2. The esterification in vitro of free cholesterol in human and rat plasma;Biochim Biophys Acta,1962
3. The plasma lecithins:cholesterol acyltransferase reaction;J Lipid Res,1968
4. Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency: effects of incubation with lecithin: cholesterol acyltransferase in vitro;Scand J Clin Lab Invest Suppl,1975
5. Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings