Effects of Administration of Recombinant Human Lecithin-Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans
Effects of Administration of Recombinant Human Lecithin-Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans
Abstract Lecithin 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.
Aikawa Masanori、Ginsberg Henry N.、Matienzo Nelsa、Baez Leinys S Santos、Hernandez-One Antonio、Yung Lau、Reyes-Soffer Gissette、Matveyenko Anastasiya、George Richard、Lignos James、Ramakrishnan Rajasekhar、Nandakumar Renu、Singh Sasha A.
Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham Women?ˉs Hospital, Harvard Medical School||Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women?ˉs Hospital, Harvard Medical School||Channing Division of Network Medicine, Department of Medicine, Brigham Women?ˉs Hospital, Harvard Medical SchoolColumbia University Vagelos College of Physicians and SurgeonsColumbia University Vagelos College of Physicians and SurgeonsColumbia University Vagelos College of Physicians and SurgeonsColumbia University Vagelos College of Physicians and SurgeonsColumbia University Vagelos College of Physicians and SurgeonsColumbia University Vagelos College of Physicians and SurgeonsColumbia University Vagelos College of Physicians and SurgeonsEarly Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&DColumbia University Vagelos College of Physicians and SurgeonsColumbia University Vagelos College of Physicians and SurgeonsColumbia University Vagelos College of Physicians and SurgeonsCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham Women?ˉs Hospital, Harvard Medical School
基础医学生物化学药学
Lipoprotein MetabolismHDL-CrhLCATApoB100
Aikawa Masanori,Ginsberg Henry N.,Matienzo Nelsa,Baez Leinys S Santos,Hernandez-One Antonio,Yung Lau,Reyes-Soffer Gissette,Matveyenko Anastasiya,George Richard,Lignos James,Ramakrishnan Rajasekhar,Nandakumar Renu,Singh Sasha A..Effects of Administration of Recombinant Human Lecithin-Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans[EB/OL].(2025-03-28)[2025-08-07].https://www.medrxiv.org/content/10.1101/2023.06.20.23291644.点此复制
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