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    651 results match your criteria Lecithin-Cholesterol Acyltransferase Deficiency

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    Depletion of HDL3 high density lipoprotein and altered functionality of HDL2 in blood from sickle cell patients.
    Exp Biol Med (Maywood) 2017 Jan 1:1535370217706966. Epub 2017 Jan 1.
    Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
    In sickle cell disease (SCD), alterations of cholesterol metabolism is in part related to abnormal levels and activity of plasma proteins such as lecithin cholesterol acyltransferase (LCAT), and apolipoprotein A-I (ApoA-I). In addition, the size distribution of ApoA-I high density lipoproteins (HDL) differs from normal blood. The ratio of the amount of HDL2 particle relative to the smaller higher density pre-β HDL (HDL3) particle was shifted toward HDL2. Read More

    Depletion in LpA-I:A-II particles enhances HDL-mediated endothelial protection in familial LCAT deficiency.
    J Lipid Res 2017 Mar 28. Epub 2017 Mar 28.
    University of Milano, Italy;
    Aim of the study was to evaluate the vasoprotective effects of HDL isolated from carriers of LCAT deficiency, which are characterized by a selective depletion of LpA-I:A-II particles and predominance of prebeta migrating HDL. HDL were isolated from LCAT deficient carriers and tested in vitro for their capacity to promote NO production and to inhibit VCAM-1 expression in cultured endothelial cells. HDL from carriers were more effective than control HDL in promoting eNOS activation with a gene-dose dependent effect (PTrend=0. Read More

    Deficient Cholesterol Esterification in Plasma of apoc2 Knockout Zebrafish and Familial Chylomicronemia Patients.
    PLoS One 2017 20;12(1):e0169939. Epub 2017 Jan 20.
    Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
    Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Apolipoprotein C-II (APOC2) is an obligatory cofactor for lipoprotein lipase (LPL), the major enzyme catalyzing plasma triglyceride hydrolysis. We have created an apoc2 knockout zebrafish model, which mimics the familial chylomicronemia syndrome (FCS) in human patients with a defect in the APOC2 or LPL gene. Read More

    [Glomerular lipidosis].
    G Ital Nefrol 2016 Malattie Metaboliche e Rene;33(S68)
    Lipidoses occur for an abnormal storage parenchymal deposition of lipids and products of their metabolism in large amounts or sometimes, involving only some particular tissue structures. The lipid storage is usually due to an inborn error causing an enzyme absence /deficiency in the primary lipidoses and to a complex metabolism alterations in the secondary forms. However, histologically all lipid depositions look very similar, and immunohistochemical investigation, clinical pictures knowledge and genetic tests need to make a correct diagnosis. Read More

    [Lecithin:Cholesterol Acyltransferase Deficiency, from genes to therapy].
    G Ital Nefrol 2016 Malattie Metaboliche e Rene;33(S68)
    LCAT synthesizes most of the plasma cholesteryl esters, and plays a major role in HDL metabolism. Mutations in the LCAT gene cause two syndromes, familial LCAT deficiency (FLD) and fish-eye disease (FED), both characterized by severe alterations in plasma lipoprotein profile. Renal disease is the major cause of morbidity and mortality in FLD cases, but an established therapy is not currently available. Read More

    Familial Lecithin Cholesterol Acyl Transferase Deficiency with Chronic Kidney Disease.
    J Assoc Physicians India 2016 Oct;64(10):90-91
    Professor, Department of Nephrology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu.
    Familial lecithin-cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive (AR) disease caused by mutation in the LCAT gene. LCAT enzyme esterifies cholesterol molecules in high-density lipoprotein(HDL) and low density-lipoprotein (LDL) particles. This enzyme deficiency is characterised by progressive corneal opacification, glomerulopathy, mild - moderate haemolytic anaemia and very low plasma levels of HDL. Read More

    Diagnosis and treatment of high density lipoprotein deficiency.
    Prog Cardiovasc Dis 2016 Sep - Oct;59(2):97-106. Epub 2016 Aug 24.
    Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA; Boston Heart Diagnostics, Framingham, MA.
    Low serum high density lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apolipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase deficiency, and fish eye disease. Read More

    Severe hypercholesterolemia and liver disease in a 3-year old.
    J Clin Lipidol 2016 May-Jun;10(3):650-3. Epub 2015 Dec 23.
    Pediatric Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, TX.
    Lipoprotein-X, which is composed of phospholipids and non-esterified cholesterol, is an abnormal lipoprotein with a density range similar to LDL-C. The two most common ways which lipoprotein-X accumulates is from reflux of bile salts into plasma or deficiency in lecithin cholesterol acyltransferase. This is a case of severe hypercholesterolemia and liver disease in a 3- year old male that presented with pruritus, pale stool, scleral ictus, and abdominal distention. Read More

    Gene-manipulated Adipocytes for the Treatment of Various Intractable Diseases.
    Yakugaku Zasshi 2016 ;136(5):705-9
    Chiba University Hospital Center for Advanced Medicine.
    Although protein replacement is an effective treatment for serum protein deficiencies such as diabetes and hemophilia, recombinant protein products are not available for all rare inherited diseases due to the instability of the recombinant proteins and/or to cost. Gene therapy is the most attractive option for treating patients with such rare diseases. To develop an effective ex vivo gene therapy-based protein replacement treatment requires recipient cells that differ from those used in standard gene therapy, which is performed to correct the function of the recipient cells. Read More

    Cellular cholesterol accumulation modulates high fat high sucrose (HFHS) diet-induced ER stress and hepatic inflammasome activation in the development of non-alcoholic steatohepatitis.
    Biochim Biophys Acta 2016 Jul 14;1861(7):594-605. Epub 2016 Apr 14.
    Keenan Research Centre, Li Ka Shing Knowledge Institute, Department of Medicine, St Michael's Hospital, Toronto, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. Electronic address:
    Non-alcoholic steatohepatitis (NASH), is the form of non-alcoholic fatty liver disease posing risk to progress into serious long term complications. Human and pre-clinical models implicate cellular cholesterol dysregulation playing important role in its development. Mouse model studies suggest synergism between dietary cholesterol and fat in contributing to NASH but the mechanisms remain poorly understood. Read More

    Endocrine Dysfunctions in Patients with Inherited Metabolic Diseases.
    J Clin Res Pediatr Endocrinol 2016 Sep 18;8(3):330-3. Epub 2016 Apr 18.
    Uludağ University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Metabolism and Endocrinology, Bursa, Turkey, E-mail:
    Objective: Inherited metabolic diseases (IMDs) can affect many organ systems, including the endocrine system. There are limited data regarding endocrine dysfunctions related to IMDs in adults, however, no data exist in pediatric patients with IMDs. The aim of this study was to investigate endocrine dysfunctions in patients with IMDs by assessing their demographic, clinical, and laboratory data. Read More

    Familial lecithin:cholesterol acyltransferase deficiency: First-in-human treatment with enzyme replacement.
    J Clin Lipidol 2016 Mar-Apr;10(2):356-67. Epub 2015 Dec 23.
    Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA.
    Background: Humans with familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) have extremely low or undetectable high-density lipoprotein cholesterol (HDL-C) levels and by early adulthood develop many manifestations of the disorder, including corneal opacities, anemia, and renal disease.

    Objective: To determine if infusions of recombinant human LCAT (rhLCAT) could reverse the anemia, halt progression of renal disease, and normalize HDL in FLD.

    Methods: rhLCAT (ACP-501) was infused intravenously over 1 hour on 3 occasions in a dose optimization phase (0. Read More

    An unusual case of nephrotic syndrome.
    Indian J Nephrol 2016 Jan-Feb;26(1):55-6
    Department of Pathology, Apollo Hospital, Telangana, Hyderabad, India.
    Nephrotic syndrome can be rarely due to inherited disorders of enzymes. One such variety is lecithin cholesterol acyltransferase deficiency. It leads to accumulation of unesterified cholesterol in the eye and other organs. Read More

    Lipoprotein X Causes Renal Disease in LCAT Deficiency.
    PLoS One 2016 26;11(2):e0150083. Epub 2016 Feb 26.
    Lipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
    Human familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Read More

    Co-existence of classic familial lecithin-cholesterol acyl transferase deficiency and fish eye disease in the same family.
    Indian J Nephrol 2015 Nov-Dec;25(6):362-5
    Department of Nephrology, PGIMER, Dr. Ram Manohar Lohia Hospital, New Delhi, India.
    We report a family with a rare genetic disorder arising out of mutation in the gene that encodes for the enzyme lecithin-cholesterol acyltransferase (LCAT). The proband presented with nephrotic syndrome, hemolytic anemia, cloudy cornea, and dyslipidemia. Kidney biopsy showed certain characteristic features to suggest LCAT deficiency, and the enzyme activity in the serum was undetectable. Read More

    Safety and Tolerability of ACP-501, a Recombinant Human Lecithin:Cholesterol Acyltransferase, in a Phase 1 Single-Dose Escalation Study.
    Circ Res 2016 Jan 1;118(1):73-82. Epub 2015 Dec 1.
    From the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD (R.D.S., A.M.S., L.A.F., M.J.A., A.W., A.T.R.); AlphaCore Pharma LLC., Ann Arbor, MI (R.B.-A., B.A., B.R.K., R.H.); VascularStrategies LLC., Plymouth Meeting, PA (S.J.A., H.L.C.); and Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD (M.S.).
    Rationale: Low high-density lipoprotein-cholesterol (HDL-C) in patients with coronary heart disease (CHD) may be caused by rate-limiting amounts of lecithin:cholesterol acyltransferase (LCAT). Raising LCAT may be beneficial for CHD, as well as for familial LCAT deficiency, a rare disorder of low HDL-C.

    Objective: To determine safety and tolerability of recombinant human LCAT infusion in subjects with stable CHD and low HDL-C and its effect on plasma lipoproteins. Read More

    Role of LCAT in Atherosclerosis.
    J Atheroscler Thromb 2016 26;23(2):119-27. Epub 2015 Nov 26.
    Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano.
    Lecithin:cholesterol acyltransferase (LCAT) is the only enzyme capable of esterifying cholesterol in plasma, thus determining the maturation of high-density lipoproteins. Because it maintains an unesterified cholesterol gradient between peripheral cells and extracellular acceptors, for a long time, LCAT has been considered as a key enzyme in reverse cholesterol transport. However, despite the fact that it has been more than 50 years since the identification of LCAT, the role of this enzyme in the pathogenesis of atherosclerosis is still debated. Read More

    Histiocytic and Nonhistiocytic Glomerular Lesions: Foam Cells and Their Mimickers.
    Am J Kidney Dis 2016 Feb 19;67(2):329-36. Epub 2015 Nov 19.
    Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. Electronic address:
    Numerous histiocytes are sometimes noted in glomeruli, giving rise to a foamy-appearing glomerulus. Foamy-appearing glomeruli may also be noted in conditions that do not contain numerous histiocytes. These disease entities are rare, have different underlying causes and pathophysiology, and can cause a diagnostic dilemma. Read More

    Update on the molecular biology of dyslipidemias.
    Clin Chim Acta 2016 Feb 4;454:143-85. Epub 2015 Nov 4.
    Department of Biochemistry, Worcester Royal Hospital, Worcester, United Kingdom.
    Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. Although secondary factors play a role in clinical expression, dyslipidemias have a strong genetic component. Familial hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the gene coding for low density lipoprotein receptor and genes encoding for proteins that interact with the receptor: APOB, PCSK9 and LDLRAP1. Read More

    Lecithin:Cholesterol Acyltransferase (LCAT) Deficiency Promotes Differentiation of Satellite Cells to Brown Adipocytes in a Cholesterol-dependent Manner.
    J Biol Chem 2015 Dec 22;290(51):30514-29. Epub 2015 Oct 22.
    From the Keenan Research Centre, Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada and the Department of Physiology, Faculty of Medicine, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Our laboratory previously reported that lecithin:cholesterol acyltransferase (LCAT) and LDL receptor double knock-out mice (Ldlr(-/-)xLcat(-/-) or DKO) spontaneously develop functioning ectopic brown adipose tissue (BAT) in skeletal muscle, putatively contributing to protection from the diet-induced obesity phenotype. Here we further investigated their developmental origin and the mechanistic role of LCAT deficiency. Gene profiling of skeletal muscle in DKO newborns and adults revealed a classical lineage. Read More

    Management of lipoprotein X and its complications in a patient with primary sclerosing cholangitis.
    Clin Lipidol 2015 Aug;10(4):305-312
    Department of Medicine, University of Chicago, Chicago, IL, 60637,USA ; Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA ; Section of Endocrinology, Diabetes & Metabolism, University of Chicago, Chicago, IL, 60637,USA.
    Lipoprotein X (LpX) is an abnormal lipoprotein found in conditions such as lecithin:cholesterol acyltransferase deficiency and cholestatic states (e.g., primary biliary cirrhosis and primary sclerosing cholangitis). Read More

    Rapid normalization of severe hypercholesterolemia mediated by lipoprotein X after liver transplantation in a patient with cholestasis - a case report.
    Acta Biochim Pol 2015 28;62(3):621-3. Epub 2015 Aug 28.
    Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland.
    Hypercholesterolemia is a common disorder in adult population, but total cholesterol concentrations beyond 1000 mg/dl occur rarely, and are found in patients with homozygous familial hypercholesterolemia and familial lecithin-cholesterol acyltransferase deficiency, in chronic graft-versus-host disease of the liver, after intravenous infusion of fat emulsion (intralipid), in newborn infants with immature liver function, and in obstructive biliary cholestasis. Cholestasis induces a dramatic increase in plasma cholesterol and the appearance of an abnormal lipoprotein, lipoprotein X (LpX), in the plasma. We report a case of severe hypercholesterolemia mediated by LpX in a patient transplanted for primary biliary cirrhosis (PBC), who was qualified for liver re-transplantation (re-LTx) due to chronic cholestasis. Read More

    Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice.
    Vascul Pharmacol 2015 Nov 5;74:114-21. Epub 2015 Aug 5.
    Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address:
    Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Read More

    Lack of LCAT reduces the LPS-neutralizing capacity of HDL and enhances LPS-induced inflammation in mice.
    Biochim Biophys Acta 2015 Oct 10;1852(10 Pt A):2106-15. Epub 2015 Jul 10.
    Pharmacology Department, University of Patras Medical School, Rio Achaias TK. 26500, Greece. Electronic address:
    HDL has important immunomodulatory properties, including the attenuation of lipopolysaccharide (LPS)-induced inflammatory response. As lecithin-cholesterol acyltransferase (LCAT) is a critical enzyme in the maturation of HDL we investigated whether LCAT-deficient (Lcat(-/-)) mice present an increased LPS-induced inflammatory response. LPS (100μg/kg body weight)-induced cytokine response in Lcat(-/-) mice was markedly enhanced and prolonged compared to wild-type mice. Read More

    Case report: A novel apolipoprotein A-I missense mutation apoA-I (Arg149Ser)Boston associated with decreased lecithin-cholesterol acyltransferase activation and cellular cholesterol efflux.
    J Clin Lipidol 2015 May-Jun;9(3):390-5. Epub 2015 Mar 5.
    Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Boston Heart Diagnostics, Framingham, MA, USA; Tufts University School of Medicine, Boston, MA, USA. Electronic address:
    We report a novel heterozygous apolipoprotein A-I (apoA-I) missense mutation (c.517C>A, p.Arg149Ser, designated as apoA-IBoston) in a 67-year-old woman and her 2 sons, who had mean serum high-density lipoprotein (HDL) cholesterol, apoA-I, and apoA-I in very large α-1 HDL that were 10%, 35%, and 16% of normal, respectively (all P < . Read More

    Response of the cholesterol metabolism to a negative energy balance in dairy cows depends on the lactational stage.
    PLoS One 2015 2;10(6):e0121956. Epub 2015 Jun 2.
    Veterinary Physiology, Vetsuisse Faculty University of Bern, Bern, Switzerland.
    The response of cholesterol metabolism to a negative energy balance (NEB) induced by feed restriction for 3 weeks starting at 100 days in milk (DIM) compared to the physiologically occurring NEB in week 1 postpartum (p.p.) was investigated in 50 dairy cows (25 control (CON) and 25 feed-restricted (RES)). Read More

    Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice.
    J Lipid Res 2015 Jul 11;56(7):1282-95. Epub 2015 May 11.
    Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
    LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results. To gain insight into LCAT and the role of free cholesterol (FC) in atherosclerosis, we examined the effect of LCAT over- and underexpression in diet-induced atherosclerosis in scavenger receptor class B member I-deficient [Scarab(-/-)] mice, which have a secondary defect in cholesterol esterification. Scarab(-/-)×LCAT-null [Lcat(-/-)] mice had a decrease in HDL-cholesterol and a high plasma ratio of FC/total cholesterol (TC) (0. Read More

    Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase.
    Nat Commun 2015 Mar 2;6:6250. Epub 2015 Mar 2.
    Life Sciences Institute and the Departments of Pharmacology and Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
    Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Read More

    Familial lecithin-cholesterol acyltransferase (LCAT) deficiency; a differential of proteinuria.
    J Nephropathol 2015 Jan 1;4(1):25-8. Epub 2015 Jan 1.
    Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.
    Background: Lecithin cholesterol acyltransferase (LCAT) is an important enzyme in cholesterol metabolism that is involved in the esterification of cholesterol. A lack of this enzyme results in deranged metabolic pathways that are not completely understood, resulting in abnormal deposition of lipids in several organs. Clinically, it manifests with proteinuria, dyslipidemia and corneal opacity with progressive chronic kidney disease resulting in end-stage renal disease. Read More

    Tissue- and sex-specific effects of β-carotene 15,15' oxygenase (BCO1) on retinoid and lipid metabolism in adult and developing mice.
    Arch Biochem Biophys 2015 Apr 17;572:11-8. Epub 2015 Jan 17.
    Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08091, USA. Electronic address:
    In mammals, β-carotene-15,15'-oxygenase (BCO1) is the main enzyme that cleaves β-carotene, the most abundant vitamin A precursor, to generate retinoids (vitamin A derivatives), both in adult and developing tissues. We previously reported that, in addition to this function, BCO1 can also influence the synthesis of retinyl esters, the storage form of retinoids, in the mouse embryo at mid-gestation. Indeed, lack of embryonic BCO1 impaired both lecithin-dependent and acyl CoA-dependent retinol esterification, mediated by lecithin:retinol acyltransferase (LRAT) and acyl CoA:retinol acyltransferase (ARAT), respectively. Read More

    A robust all-atom model for LCAT generated by homology modeling.
    J Lipid Res 2015 Mar 14;56(3):620-34. Epub 2015 Jan 14.
    Center for Computational and Structural Dynamics University of Alabama at Birmingham, Birmingham, AL 35294-0012 Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-0012.
    LCAT is activated by apoA-I to form cholesteryl ester. We combined two structures, phospholipase A2 (PLA2) that hydrolyzes the ester bond at the sn-2 position of oxidized (short) acyl chains of phospholipid, and bacteriophage tubulin PhuZ, as C- and N-terminal templates, respectively, to create a novel homology model for human LCAT. The juxtaposition of multiple structural motifs matching experimental data is compelling evidence for the general correctness of many features of the model: i) The N-terminal 10 residues of the model, required for LCAT activity, extend the hydrophobic binding trough for the sn-2 chain 15-20 Å relative to PLA2. Read More

    Tubulointerstitial nephritis is a dominant feature of hereditary apolipoprotein A-I amyloidosis.
    Kidney Int 2015 Jun 7;87(6):1223-9. Epub 2015 Jan 7.
    Division of Nephrology and Dialysis, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Montichiari Hospital, Brescia, Italy.
    Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and is encoded by the APOA1 gene. Several APOA1 mutations have been found, either affecting the lecithin:cholesterol acyltransferase activity, determining familial HDL deficiency, or resulting in amyloid formation with prevalent deposits in the kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of 253 carriers belonging to 50 families from Brescia, Italy. Read More

    A Western-fed diet increases plasma HDL and LDL-cholesterol levels in apoD-/- mice.
    PLoS One 2014 30;9(12):e115744. Epub 2014 Dec 30.
    The City College of New York, Biology Department, New York, New York, United States of America.
    Objective: Plasma apolipoprotein (apo)D, a ubiquitously expressed protein that binds small hydrophobic ligands, is found mainly on HDL particles. According to studies of human genetics and lipid disorders, plasma apoD levels positively correlate with HDL-cholesterol and apoAI levels. Thus, we tested the hypothesis that apoD was a regulator of HDL metabolism. Read More

    Mouse models of disturbed HDL metabolism.
    Handb Exp Pharmacol 2015 ;224:301-36
    Division of Biopharmaceutics, Gorlaeus Laboratories, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC, Leiden, The Netherlands,
    High-density lipoprotein (HDL) is considered to be an anti-atherogenic lipoprotein moiety. Generation of genetically modified (total body and tissue-specific knockout) mouse models has significantly contributed to our understanding of HDL function. Here we will review data from knockout mouse studies on the importance of HDL's major alipoprotein apoA-I, the ABC transporters A1 and G1, lecithin:cholesterol acyltransferase, phospholipid transfer protein, and scavenger receptor BI for HDL's metabolism and its protection against atherosclerosis in mice. Read More

    Differences in reaction specificity toward lipoprotein X and abnormal LDL among 6 homogeneous assays for LDL-cholesterol.
    Clin Chim Acta 2015 Jan 5;439:29-37. Epub 2014 Oct 5.
    Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
    Background: We investigated the reaction specificity toward cholesterol in lipoprotein X (Lp-X) and abnormal LDL among 6 homogeneous assays for low-density lipoprotein cholesterol (LDL-C) based on different measurement principles.

    Methods: The homogeneous LDL-C assays used were based on the liquid selective detergent, selective solubilization, elimination, enzyme-selective protection, calixarene complex, and phosphate complex inhibition methods. The fraction with a density of 1. Read More

    A review on lecithin:cholesterol acyltransferase deficiency.
    Clin Biochem 2015 May 27;48(7-8):472-5. Epub 2014 Aug 27.
    Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, Canada. Electronic address:
    Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme which esterifies cholesterol, and plays a key role in the metabolism of high-density lipoprotein cholesterol (HDL-C). Genetic disorders of LCAT are associated with lipoprotein abnormalities including low levels of HDL-C and presence of lipoprotein X, and clinical features mainly corneal opacities, changes in erythrocyte morphology and renal failure. Recombinant LCAT is being developed for the treatment of patients with LCAT deficiency. Read More

    Acquired lecithin:cholesterol acyltransferase deficiency as a major factor in lowering plasma HDL levels in chronic kidney disease.
    J Intern Med 2015 May 1;277(5):552-61. Epub 2014 Aug 1.
    Center E. Grossi Paoletti, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
    Objectives: It has been suggested that a low plasma high-density lipoprotein cholesterol (HDL-C) level contributes to the high cardiovascular disease risk of patients with chronic kidney disease (CKD), especially those undergoing haemodialysis (HD). The present study was conducted to gain further understanding of the mechanism(s) responsible for the low HDL-C levels in patients with CKD and to separate the impact of HD from that of the underlying CKD.

    Methods: Plasma lipids and lipoproteins, HDL subclasses and various cholesterol esterification parameters were measured in a total of 248 patients with CKD, 198 of whom were undergoing HD treatment and 40 healthy subjects. Read More

    LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice.
    J Lipid Res 2014 Aug 20;55(8):1721-9. Epub 2014 Jun 20.
    Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
    A key step in plasma HDL maturation from discoidal to spherical particles is the esterification of cholesterol to cholesteryl ester, which is catalyzed by LCAT. HDL-like lipoproteins in cerebrospinal fluid (CSF) are also spherical, whereas nascent lipoprotein particles secreted from astrocytes are discoidal, suggesting that LCAT may play a similar role in the CNS. In plasma, apoA-I is the main LCAT activator, while in the CNS, it is believed to be apoE. Read More

    Lipoprotein subfractions highly associated with renal damage in familial lecithin:cholesterol acyltransferase deficiency.
    Arterioscler Thromb Vasc Biol 2014 Aug 29;34(8):1756-62. Epub 2014 May 29.
    From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.).
    Objective: In familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD), deposition of abnormal lipoproteins in the renal stroma ultimately leads to renal failure. However, fish-eye disease (FED) does not lead to renal damage although the causative mutations for both FLD and FED lie within the same LCAT gene. This study was performed to identify the lipoproteins important for the development of renal failure in genetically diagnosed FLD in comparison with FED, using high-performance liquid chromatography with a gel filtration column. Read More

    High-density lipoprotein metabolism, composition, function, and deficiency.
    Curr Opin Lipidol 2014 Jun;25(3):194-9
    Lipid Metabolism Section, Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA.
    Purpose Of Review: To examine the recent advances in our knowledge of HDL metabolism, composition, function, and coronary heart disease (CHD), as well as marked HDL deficiency states because of mutations in the apolipoprotein (apo) A-I, ATP-binding cassette transfer protein A1 and lecithin cholesterol acyltransferase (LCAT) gene loci.

    Recent Findings: It has been documented that apoA-I, myeloperoxidase and paraoxonase 1 (PON1) form a complex in HDL that is critical for HDL binding and function. Myeloperoxidase has a negative impact on HDL function, whereas PON1 has a beneficial effect. Read More

    A kindred with fish eye disease, corneal opacities, marked high-density lipoprotein deficiency, and statin therapy.
    J Clin Lipidol 2014 Mar-Apr;8(2):223-30. Epub 2013 Dec 11.
    Boston Heart Diagnostics, Framingham, MA, USA; Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA, USA.
    A kindred affected with fish eye disease (FED) from Oklahoma is reported. Two probands with corneal opacification had mean levels of high-density lipoprotein (HDL) cholesterol (C), apolipoprotein (apo) A-I, and apoA-I in very large alpha-1 HDL particles that were 9%, 17%, and 5% of normal, whereas their parents and 1 sibling had values that were 61%, 77%, and 72% of normal. The probands had no detectable lipoprotein-X, and had mean low-density lipoprotein cholesterol (LDL-C) and triglyceride levels that were elevated. Read More

    Scavenger receptor BI and high-density lipoprotein regulate thymocyte apoptosis in sepsis.
    Arterioscler Thromb Vasc Biol 2014 May 6;34(5):966-75. Epub 2014 Mar 6.
    From the Department of Pediatrics (L.G., Z.Z., J.A., X.-A.L.), Graduate Center for Nutritional Sciences (Z.Z., J.A., X.-A.L.), and Saha Cardiovascular Research Center (D.A.H., A.D., X.-A.L.), University of Kentucky College of Medicine, Lexington; and Laboratory of Immune Cell Biology, National Cancer Institute (P.R.M., J.D.A.) and Lipoprotein Metabolism Section, National Heart, Lung, and Blood Institute (S.T., A.T.R.), National Institutes of Health, Bethesda, MD.
    Objective: Thymocyte apoptosis is a major event in sepsis; however, how this process is regulated remains poorly understood.

    Approach And Results: Septic stress induces glucocorticoids production which triggers thymocyte apoptosis. Here, we used scavenger receptor BI (SR-BI)-null mice, which are completely deficient in inducible glucocorticoids in sepsis, to investigate the regulation of thymocyte apoptosis in sepsis. Read More

    Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects.
    Cardiovasc Diabetol 2013 Nov 22;12:173. Epub 2013 Nov 22.
    Lipids Laboratory (LIM-10), Endocrinology and Metabolism Division of Hospital das Clinicas, Faculty of Medical Sciences, University of Sao Paulo, Av, Dr, Arnaldo, 455 - room 3305, Sao Paulo CEP 01246-00, Brazil.
    Background: We have searched if plasma high density lipoprotein-cholesterol (HDL-C) concentration interferes simultaneously with whole-body cholesterol metabolism and insulin sensitivity in normal weight healthy adult subjects.

    Methods: We have measured the activities of several plasma components that are critically influenced by insulin and that control lipoprotein metabolism in subjects with low and high HDL-C concentrations. These parameters included cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), lecithin cholesterol acyl transferase (LCAT), post-heparin lipoprotein lipase (LPL), hepatic lipase (HL), pre-beta-₁HDL, and plasma sterol markers of cholesterol synthesis and intestinal absorption. Read More

    Pharmacological interventions in human HDL metabolism.
    Curr Opin Lipidol 2013 Dec;24(6):500-9
    aDepartment of Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands bUniversité de Lille 2 cInserm, U1011 dInstitut Pasteur de Lille eEuropean Genomic Institute for Diabetes (EGID), FR 3508, Lille, France.
    Purpose Of Review: This review focuses on the recent developments in the field of drugs that affect HDL metabolism. Additionally, some general (retrospective) thoughts on fighting cardiovascular disease through modulating circulating lipids are discussed.

    Recent Findings: Recently, the large 'Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes', 'Treatment of HDL to Reduce the Incidence of Vascular Events' and dal-OUTCOMES studies have challenged the idea that raising HDL cholesterol (HDL-c) decreases cardiovascular disease risk. Read More

    Characteristic kidney pathology, gene abnormality and treatments in LCAT deficiency.
    Clin Exp Nephrol 2014 Apr 31;18(2):189-93. Epub 2013 Oct 31.
    Department of Nephrology, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
    Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme involved in reverse cholesterol transport from the peripheral tissues to the liver. LCAT deficiency, in which this enzyme is congenitally absent, is a genetic disease that impairs the esterification of free cholesterol in the plasma, leading to accumulation of phospholipids, including lecithin, in the organs of the body; the clinical manifestations include corneal opacities, normochromic anemia, renal disorder, etc. The prognosis is determined by the degree of renal dysfunction, and renal biopsy specimens reveal characteristic light- and electron-microscopic findings. Read More

    Recombinant human LCAT normalizes plasma lipoprotein profile in LCAT deficiency.
    Biologicals 2013 Nov 18;41(6):446-9. Epub 2013 Oct 18.
    Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
    Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. Mutations in the LCAT gene leads to two rare disorders, familial LCAT deficiency and fish-eye disease, both characterized by severe hypoalphalipoproteinemia associated with several lipoprotein abnormalities. No specific treatment is presently available for genetic LCAT deficiency. Read More

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