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J Atheroscler Thromb 2021 Apr 18. Epub 2021 Apr 18.

Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center Research Institute.

Lecithin cholesterol acyltransferase (LCAT) is a lipid-modification enzyme that catalyzes the transfer of the acyl chain from the second position of lecithin to the hydroxyl group of cholesterol (FC) on plasma lipoproteins to form cholesteryl acylester and lysolecithin. Familial LCAT deficiency is an intractable autosomal recessive disorder caused by inherited dysfunction of the LCAT enzyme. The disease appears in two different phenotypes depending on the position of the gene mutation: familial LCAT deficiency (FLD, OMIM 245900) that lacks esterification activity on both HDL and ApoB-containing lipoproteins, and fish-eye disease (FED, OMIM 136120) that lacks activity only on HDL. Read More

Cells 2021 Mar 31;10(4). Epub 2021 Mar 31.

Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, Italy.

Dyslipidemia is a typical trait of patients with chronic kidney disease (CKD) and it is typically characterized by reduced high-density lipoprotein (HDL)-cholesterol(c) levels. The low HDL-c concentration is the only lipid alteration associated with the progression of renal disease in mild-to-moderate CKD patients. Plasma HDL levels are not only reduced but also characterized by alterations in composition and structure, which are responsible for the loss of atheroprotective functions, like the ability to promote cholesterol efflux from peripheral cells and antioxidant and anti-inflammatory proprieties. Read More

Ann Intern Med 2021 Mar 2. Epub 2021 Mar 2.

Institut National de la Science et de la Recherche Médicale, INSERM U1297-Institut des Maladies Métaboliques et Cardiovasculaires, and Université Paul Sabatier-Toulouse III, Toulouse, France.

Metabolism 2021 03 9;116:154464. Epub 2020 Dec 9.

Center E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy. Electronic address:

Objective: CER-001 is an HDL mimetic that has been tested in different pathological conditions, but never with LCAT deficiency. This study was designed to investigate whether the absence of LCAT affects the catabolic fate of CER-001, and to evaluate the effects of CER-001 on kidney disease associated with LCAT deficiency.

Methods: Lcat and wild-type mice received CER-001 (2. Read More

World J Hepatol 2020 Oct;12(10):722-737

Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia.

Combined liver and kidney transplantation (CLKT) is indicated in patients with failure of both organs, or for the treatment of end-stage chronic kidney disease (ESKD) caused by a genetic defect in the liver. The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT. They are major indications for CLKT in children. Read More

Arterioscler Thromb Vasc Biol 2021 01 22;41(1):360-376. Epub 2020 Oct 22.

Discovery Science and Technology Department (H.S., Y.F., N.W., K.K.), Daiichi Sankyo RD Novare, Co, Ltd, Tokyo, Japan.

Objective: Enhancement of LCAT (lecithin:cholesterol acyltransferase) activity has possibility to be beneficial for atherosclerosis. To evaluate this concept, we characterized our novel, orally administered, small-molecule LCAT activator DS-8190a, which was created from high-throughput screening and subsequent derivatization. We also focused on its mechanism of LCAT activation and the therapeutic activity with improvement of HDL (high-density lipoprotein) functionality. Read More

J Lipid Res 2020 12 30;61(12):1784-1788. Epub 2020 Sep 30.

Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy. Electronic address:

Familial LCAT deficiency (FLD) is a rare genetic disorder of HDL metabolism, caused by loss-of-function mutations in the gene and characterized by a variety of symptoms including corneal opacities and kidney failure. Renal disease represents the leading cause of morbidity and mortality in FLD cases. However, the prognosis is not known and the rate of deterioration of kidney function is variable and unpredictable from patient to patient. Read More

Arterioscler Thromb Vasc Biol 2020 12 1;40(12):2829-2836. Epub 2020 Oct 1.

Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education (M.G., P.M., W.H., Y.W., G.L., X.X.), Peking University, Beijing, China.

Objective: LCAT (lecithin cholesterol acyltransferase) deficiency results in severe low HDL (high-density lipoprotein). Although whether LCAT is pro- or antiatherosclerosis was in debate in mouse studies, our previous study clearly shows that LCAT deficiency (LCAT) in hamster accelerates atherosclerotic development on high-fat diet. However, unlike in hypercholesterolemia and hypertriglyceridemia, whether LCAT deficiency could lead to spontaneous atherosclerosis has not been studied yet in animal models. Read More

J Pharmacol Exp Ther 2020 12 26;375(3):463-468. Epub 2020 Sep 26.

Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari (C.P., A.O., M.T., A.S., S.S., L.C.) and Dipartimento di Scienze Farmacologiche e Biomolecolari (T.L., I.E.), Università degli Studi di Milano, Milan, Italy; Specialty Medicine Research Laboratories I, Daiichi Sankyo Co., Ltd., Tokyo, Japan (K.K., N.K.); and Medical Affairs Planning Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan (K.Y.)

Lecithin:cholesterol acyltransferase (LCAT) is a unique plasma enzyme able to esterify cholesterol, and it plays an important role in HDL maturation and promotion of reverse cholesterol transport. Familial LCAT deficiency (FLD; OMIM number 245900) is a rare recessive disease that results from loss-of-function mutations in the gene and has no cure. In this study, we assessed the in vitro efficacy of a novel small-molecule LCAT activator. Read More

J Lipid Res 2020 09 19;61(9):1287-1299. Epub 2020 Jun 19.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University, Shimotsuke 329-0498, Japan

The acyltransferase LCAT mediates FA esterification of plasma cholesterol. In vitro studies have shown that LCAT also FA-esterifies several oxysterols, but in vivo evidence is lacking. Here, we measured both free and FA-esterified forms of sterols in 206 healthy volunteers and 8 individuals with genetic LCAT deficiency, including familial LCAT deficiency (FLD) and fish-eye disease (FED). Read More

J Lipid Res 2020 08 1;61(8):1142-1149. Epub 2020 Jun 1.

Department of Nutrition, University of Oslo, Oslo, Norway

LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. Read More

Curr Opin Lipidol 2020 04;31(2):71-79

Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda.

Purpose Of Review: To review recent lecithin:cholesterol acyltransferas (LCAT)-based therapeutic approaches for atherosclerosis, acute coronary syndrome, and LCAT deficiency disorders.

Recent Findings: A wide variety of approaches to using LCAT as a novel therapeutic target have been proposed. Enzyme replacement therapy with recombinant human LCAT is the most clinically advanced therapy for atherosclerosis and familial LCAT deficiency (FLD), with Phase I and Phase 2A clinical trials recently completed. Read More

FASEB J 2020 03 23;34(3):3805-3819. Epub 2020 Jan 23.

Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences, Wuhan, China.

High-density lipoprotein (HDL), a well-known atheroprotective factor, can be converted to proatherogenic particles in chronic inflammation. HDL-targeted therapeutic strategy for atherosclerotic cardiovascular disease (CVD) is currently under development. This study aims to assess the role of methionine sulfoxide reductase A (MsrA) in abnormal HDL and its related disorders in scavenger receptor class B type I deficient (SR-BI ) mice. Read More

Pharmacol Res Perspect 2020 02 29;8(1):e00554. Epub 2019 Dec 29.

Lipoprotein Metabolism Section Translational Vascular Medicine Branch National Heart Lung and Blood Institute National Institutes of Health Bethesda MD USA.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disease characterized by low HDL-C levels, low plasma cholesterol esterification, and the formation of Lipoprotein-X (Lp-X), an abnormal cholesterol-rich lipoprotein particle. LCAT deficiency causes corneal opacities, normochromic normocytic anemia, and progressive renal disease due to Lp-X deposition in the glomeruli. Recombinant LCAT is being investigated as a potential therapy for this disorder. Read More

Biomolecules 2019 11 26;9(12). Epub 2019 Nov 26.

Experimental Atherosclerosis Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Lecithin:cholesterol acyltransferase (LCAT) is an enzyme secreted by the liver and circulates with high-density lipoprotein (HDL) in the blood. The enzyme esterifies plasma cholesterol and increases the capacity of HDL to carry and potentially remove cholesterol from tissues. Cholesterol accumulates within the extracellular connective tissue matrix of the cornea stroma in individuals with genetic deficiency of LCAT. Read More

Internist (Berl) 2019 Dec;60(12):1311-1318

Institut für Klinische Chemie, Universitätsspital Zürich und Universität Zürich, Rämistrasse 100, 8091, Zürich, Schweiz.

Both low and very high levels of high-density lipoprotein cholesterol (HDL-C) increase the risk of atherosclerotic cardiovascular disease (ASCVD) and shorten life expectancy. Low and high levels of HDL‑C are often caused by underlying diseases, lifestyle or medication, which should primarily be excluded. Much less frequently, monogenic diseases due to mutations in the APOA1, ABCA1 and LCAT genes are the cause of very low or unmeasurable HDL‑C levels or in the CETP, LIPC and SCARB1 genes for very high HDL‑C values. Read More

J Clin Med 2019 Nov 3;8(11). Epub 2019 Nov 3.

Lipid Unit, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBER Cardiovascular (CIBERCV), 50009 Zaragoza, Spain.

Renal complications are the major cause of morbidity and mortality in patients with familial lecithin-cholesterol acyltransferase (LCAT) deficiency (FLD). We report three FLD patients, two of them siblings-only one of whom developed renal disease-and the third case being a young man with early renal disease. The aim of this study was to analyze the clinical characteristics and possible mechanisms associated with renal disease in these patients. Read More

Clin Med Insights Endocrinol Diabetes 2019 29;12:1179551419878687. Epub 2019 Sep 29.

Endocrinology Section, Fundación Santa Fe de Bogotá, Bogotá, Colombia.

The liver is a key organ in lipid and lipoprotein metabolism, hence hepatic diseases often manifest as lipid disturbances. Cholestatic liver diseases are frequently associated with an important increase in total cholesterol at the expense of lipoprotein X (LpX), an abnormal lipoprotein isolated and characterized in the 1960s to 1970s in patients with obstructive jaundice. Lipoprotein X is rich in phospholipids, albumin, and free cholesterol, has a density similar to low-density lipoprotein (LDL), and a size similar to very low-density lipoprotein (VLDL), which has hampered its detection through routine laboratory tests. Read More

J Atheroscler Thromb 2020 Jan 4;27(1):4-5. Epub 2019 Sep 4.

Research Institute for Physical Activity, Fukuoka University.

Lipids Health Dis 2019 Jun 5;18(1):132. Epub 2019 Jun 5.

Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.

Background: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. Read More

Am J Kidney Dis 2019 10 15;74(4):510-522. Epub 2019 May 15.

Nephrology Department, Heraklion University Hospital, Crete, Greece. Electronic address:

Rationale & Objective: Lecithin-cholesterol acyltransferase (LCAT) catalyzes the maturation of high-density lipoprotein. Homozygosity for loss-of-function mutations causes familial LCAT deficiency (FLD), characterized by corneal opacities, anemia, and renal involvement. This study sought to characterize kidney biopsy findings and clinical outcomes in a family with FLD. Read More

J Atheroscler Thromb 2020 Jan 14;27(1):25-37. Epub 2019 May 14.

Institute of Biological Functions, Chubu University.

Aim: Probucol is a controversial drug to inhibit ATP-binding cassette transporter A1 (ABCA1) and to exhibit some positive clinical effects such as regression of xanthomas. It reportedly rescues female infertility in scavenger receptor BI-deficient mice. Here, we investigated the effect of probucol on propagation in HDL-deficient mice as alternative models for impaired HDL-mediated cholesterol delivery. Read More

J Lipid Res 2019 05 26;60(5):1050-1057. Epub 2019 Feb 26.

Translational Vascular Medicine Branch National Institutes of Health, Bethesda, MD; the NIH Clinical Center National Institutes of Health, Bethesda, MD.

Familial LCAT deficiency (FLD) patients accumulate lipoprotein-X (LP-X), an abnormal nephrotoxic lipoprotein enriched in free cholesterol (FC). The low neutral lipid content of LP-X limits the ability to detect it after separation by lipoprotein electrophoresis and staining with Sudan Black or other neutral lipid stains. A sensitive and accurate method for quantitating LP-X would be useful to examine the relationship between plasma LP-X and renal disease progression in FLD patients and could also serve as a biomarker for monitoring recombinant human LCAT (rhLCAT) therapy. Read More

Biochim Biophys Acta Mol Basis Dis 2019 06 10;1865(6):1351-1360. Epub 2019 Feb 10.

University of Patras, School of Medicine, Department of Pharmacology, Rio, Achaias, TK. 26500, Greece. Electronic address:

High density lipoprotein (HDL) has attracted the attention of biomedical community due to its well-documented role in atheroprotection. HDL has also been recently implicated in the regulation of islets of Langerhans secretory function and in the etiology of peripheral insulin sensitivity. Indeed, data from numerous studies strongly indicate that the functions of pancreatic β-cells, skeletal muscles and adipose tissue could benefit from improved HDL functionality. Read More

Curr Opin Endocrinol Diabetes Obes 2019 04;26(2):117-123

Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Purpose Of Review: Lipoprotein-X (Lp-X) is an abnormal lipoprotein containing abundant free cholesterol and phospholipids, as well as some apolipoprotein E (apoE). Serum Lp-X increases in patients with cholestasis and lecithin-cholesterol acyltransferase deficiency, as well as in those receiving intravenous lipid emulsion. Lp-X is often associated with skin xanthomas in cholestatic patients. Read More

Optom Vis Sci 2019 02;96(2):137-141

Edward S. Harkness Eye Institute, Columbia University Medical Center, New York, New York

Significance: Given that there are few reported cases of lecithin:cholesterol acyltransferase (LCAT) deficiency, recognition of the condition with proper management is notable. Long-term follow-up and contact lens fitting after penetrating keratoplasty provide best possible outcomes.

Purpose: The purpose of this study was to report a case of LCAT deficiency successfully treated with penetrating keratoplasty and longer-term follow-up with contact lens fitting. Read More

J Pharmacol Exp Ther 2019 03 18;368(3):423-434. Epub 2018 Dec 18.

Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (B.L.V., E.B.N., L.A.F., S.M.G., M.L.S., M.P., E.H., A.T.R.) and MedImmune, Gaithersburg, Maryland (M.J.A., S.K.K.).

Familial LCAT deficiency (FLD) is due to mutations in lecithin:cholesterol acyltransferase (LCAT), a plasma enzyme that esterifies cholesterol on lipoproteins. FLD is associated with markedly reduced levels of plasma high-density lipoprotein and cholesteryl ester and the formation of a nephrotoxic lipoprotein called LpX. We used a mouse model in which the LCAT gene is deleted and a truncated version of the SREBP1a gene is expressed in the liver under the control of a protein-rich/carbohydrate-low (PRCL) diet-regulated PEPCK promoter. Read More

Ann Pathol 2019 Apr 12;39(2):172-176. Epub 2018 Dec 12.

Service d'anatomie et cytologie pathologiques, hôpital Timone, 264, rue Saint-Pierre, 13005 Marseille, France; Inserm U1263, C2VN, Aix Marseille université, 13006 Marseille, France.

Glomerulopathy associated with lecithin-cholesterol-acyltransferase deficiency (LCAT) is a rare automosal recessive disease. Acquired LCAT deficiency due to inhibitory autoantibodies against LCAT are also described. This disease is induced by systemic deposits related to a lipid metabolism disorder and lead to multi-organ involvement including renal involvement. Read More

J Proteomics 2019 04 6;198:113-118. Epub 2018 Dec 6.

Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Italy. Electronic address:

Genetic LCAT deficiency is a rare recessive autosomal disease due to loss-of-function mutations in the gene coding for the enzyme lecithin:cholesterol acyltransferase (LCAT). Homozygous carriers are characterized by corneal opacity, haemolytic anaemia and renal disease, which represent the first cause of morbidity and mortality in these subjects. Diagnostic and prognostic markers capable of early detecting declining kidney function in these subjects are not available, and the specific serum or urine proteomic signature of LCAT deficient carriers has never been assessed. Read More

J Cell Biochem 2018 Dec 2. Epub 2018 Dec 2.

Genetic laboratory of Amirkola Children's Hospital, Babol University of Medical Sciences, Babol, Iran.

Introduction: Lecithin cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder occurred by different mutations in the LCAT gene that cause two extremely rare syndromes including familial LCAT deficiency (FLD) and fish-eye disease (FED). Unlike FED in FLD renal failure is the most important defect due to deposition of abnormal lipoproteins in the renal stroma. In this study, FLD patients from the North of Iran were investigated for mutations in the LCAT gene. Read More