ArticleMetabolism: clinical and experimental2009
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.
Article in Metabolism: clinical and experimental, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Effects of Recombinant Human Lecithin Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans.Arteriosclerosis, thrombosis, and vascular biology · 2024Trial
- MEDI6012: Recombinant Human Lecithin Cholesterol Acyltransferase, High-Density Lipoprotein, and Low-Density Lipoprotein Receptor-Mediated Reverse Cholesterol Transport.Journal of the American Heart Association · 2021Trial
- Depleting LCAT Aggravates Atherosclerosis in LDLR-deficient Hamster with Reduced LDL-Cholesterol Level.Journal of advanced research · 2024Article
- Two novel variants in the lecithin:cholesterol acyltransferase gene resulted in classic LCAT deficiency.Atherosclerosis plus · 2022Article
- Apolipoprotein A1-Related Proteins and Reverse Cholesterol Transport in Antiatherosclerosis Therapy: Recent Progress and Future Perspectives.Cardiovascular therapeutics · 2022Review
- Progression of chronic kidney disease in familial LCAT deficiency: a follow-up of the Italian cohort.Journal of lipid research · 2020Article
- Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings.Journal of lipid research · 2020Article
- Novel lecithin: cholesterol acyltransferase-based therapeutic approaches.Current opinion in lipidology · 2020Article
- HDL Cholesterol Metabolism and the Risk of CHD: New Insights from Human Genetics.Current cardiology reports · 2017Review
- Role of apolipoproteins, ABCA1 and LCAT in the biogenesis of normal and aberrant high density lipoproteins.Journal of biomedical research · 2017Article
- Deficient Cholesterol Esterification in Plasma of apoc2 Knockout Zebrafish and Familial Chylomicronemia Patients.PloS one · 2017Article
- Safety and Tolerability of ACP-501, a Recombinant Human Lecithin:Cholesterol Acyltransferase, in a Phase 1 Single-Dose Escalation Study.Circulation research · 2016Article
- Endemic Viruses of Squirrel Monkeys (Saimiri spp.).Comparative medicine · 2015Review
- Recombinant human lecithin-cholesterol acyltransferase Fc fusion: analysis of N- and O-linked glycans and identification and elimination of a xylose-based O-linked tetrasaccharide core in the linker region.Protein science : a publication of the Protein Society · 2013Article
- Role of the hydrophobic and charged residues in the 218-226 region of apoA-I in the biogenesis of HDL.Journal of lipid research · 2013Article
- Lecithin:cholesterol acyltransferase: old friend or foe in atherosclerosis?Journal of lipid research · 2012Review
- Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport.Circulation · 2012Review
- AAV8-mediated long-term expression of human LCAT significantly improves lipid profiles in hCETP;Ldlr(+/-) mice.Journal of cardiovascular translational research · 2011Article
- Lecithin cholesterol acyltransferase: an anti- or pro-atherogenic factor?Current atherosclerosis reports · 2011Review
- Plasma levels of lecithin:cholesterol acyltransferase and risk of future coronary artery disease in apparently healthy men and women: a prospective case-control analysis nested in the EPIC-Norfolk population study.Journal of lipid research · 2010Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Lecithin-cholesterol acyltransferase (LCAT), a key enzyme in high-density lipoprotein (HDL) metabolism, has been proposed to have atheroprotective properties by promoting reverse cholesterol transport. Overexpression of LCAT in various animal models, however, has led to conflicting results on its overall effect on lipoproteins and atherosclerosis. In this study, the effect of overexpression of LCAT in nonhuman primates on lipoprotein metabolism is examined. Human LCAT was expressed with adenovirus in squirrel monkeys (n = 8), resulting on day 4 in a 22-fold increase of LCAT activity (257 +/- 23 vs 5618 +/- 799 nmol mL(-1) h(-1), P < .0001). At its peak, LCAT was found to nearly double the level of HDL cholesterol from baseline (113 +/- 7 vs 260 +/- 24 mg/dL, P < .01). High-density lipoprotein formed after treatment with the adenovirus was larger in size, as assessed by fast protein liquid chromatography (FPLC) analysis. By kinetic studies, it was determined that there was a decrease in apolipoprotein (Apo) A-I resident time (0.373 +/- 0.027 vs 0.685 +/- 0.045 d(-1), P < .0001) and almost a doubling in the ApoA-I synthetic rate (22 +/- 2 vs 41 +/- 3 mg kg(-1) d(-1), P < .0001), but no overall change in ApoA-I levels. In addition, increased expression of LCAT was associated with a 37% reduction of ApoB levels (12 +/- 1 vs 19 +/- 1 mg/dL, P < .05) due to increased low-density lipoprotein catabolism (fractional catabolic rate = 1.7 +/- 0.1 d(-1) in controls vs 4.2 +/- 0.3 d(-1) in LCAT-treated group, P < .05). In summary, overexpression of LCAT in nonhuman primates leads to an antiatherogenic lipoprotein profile by increasing HDL cholesterol and lowering ApoB, thus making LCAT a potential drug target for reducing atherosclerosis.
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