Effects of Recombinant Human Lecithin Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans

Author:

Reyes-Soffer Gissette1ORCID,Matveyenko Anastasiya1,Lignos James1,Matienzo Nelsa1ORCID,Santos Baez Leinys S.1ORCID,Hernandez-Ono Antonio1ORCID,Yung Lau1,Nandakumar Renu2,Singh Sasha A.3ORCID,Aikawa Masanori345ORCID,George Richard6ORCID,Ginsberg Henry N.1ORCID

Affiliation:

1. Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York (G.R.-S., A.M., J.L., N.M., L.S.S.B., A.H.-O., L.Y., H.N.G.).

2. Irving Institute for Clinical and Translations Research (R.N.) and Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York.

3. Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine (S.A.S., M.A.), Brigham Women’s Hospital, Harvard Medical School, Boston, MA.

4. Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine (M.A.), Brigham Women’s Hospital, Harvard Medical School, Boston, MA.

5. Channing Division of Network Medicine, Department of Medicine (M.A.), Brigham Women’s Hospital, Harvard Medical School, Boston, MA.

6. Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD (R.G.).

Abstract

BACKGROUND: LCAT (lecithin cholesterol acyl transferase) catalyzes the conversion of unesterified, or free cholesterol, to cholesteryl ester, which moves from the surface of HDL (high-density lipoprotein) into the neutral lipid core. As this iterative process continues, nascent lipid-poor HDL is converted to a series of larger, spherical cholesteryl ester–enriched HDL particles that can be cleared by the liver in a process that has been termed reverse cholesterol transport. METHODS: We conducted a randomized, placebocontrolled, crossover study in 5 volunteers with atherosclerotic cardiovascular disease, to examine the effects of an acute increase of recombinant human (rh) LCAT via intravenous administration (300-mg loading dose followed by 150 mg at 48 hours) on the in vivo metabolism of HDL APO (apolipoprotein)A1 and APOA2, and the APOB100-lipoproteins, very low density, intermediate density, and low-density lipoproteins. RESULTS: As expected, recombinant human LCAT treatment significantly increased HDL-cholesterol (34.9 mg/dL; P ≤0.001), and this was mostly due to the increase in cholesteryl ester content (33.0 mg/dL; P =0.014). This change did not affect the fractional clearance or production rates of HDL-APOA1 and HDL-APOA2. There were also no significant changes in the metabolism of APOB100-lipoproteins. CONCLUSIONS: Our results suggest that an acute increase in LCAT activity drives greater flux of cholesteryl ester through the reverse cholesterol transport pathway without significantly 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

Ovid Technologies (Wolters Kluwer Health)

Reference38 articles.

1. Santamarina-Fojo, S, Hoeg, JM, Assmann, G, Bryan Brewer, HH, Jr. Lecithin cholesterol acyltransferase deficiency and fish eye disease. In: Valle, DL, Antonarakis, S, Ballabio, A, Beaudet, AL, Mitchell, GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill Education; 2019. Accessed May 8, 2024. https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225539713

2. The esterification in vitro of free cholesterol in human and rat plasma

3. The plasma lecithin:cholesterol acyltransferase reaction

4. Plasma lipoproteins in familial lecithin:cholesterol acyltransferase deficiency: lipid composition and reactivity in vitro

5. 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

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