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J Clin Lipidol 2021 Jan-Feb;15(1):142-150.e2. Epub 2020 Dec 24.

Division of Chemical Pathology, University of Cape Town Faculty of Health Sciences, Anzio Road, Observatory, 7925, Cape Town, South Africa. Electronic address:

Background: High density lipoprotein cholesterol (HDL-C) concentration correlates inversely with atherosclerotic cardiovascular disease (ASCVD) risk and is included in risk calculations. Endothelial lipase (EL) is a phospholipase that remodels HDL. Deficiency of EL due to mutations in its gene, LIPG, is associated with hyperalphalipoproteinemia. Read More

J Med Biochem 2020 Sep;39(3):372-383

National Research Centre for Preventive Medicine, Laboratory of Structural Fundamentals of Lipoprotein Metabolism, Moscow, Russia.

Background: To reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in peripheral blood mononuclear cells (PBMC) and involved in HDL metabolism and atherogenesis at the absence of morphologically evident coronary stenosis.

Methods: Transcript levels of 63 genes in PBMC from 38 male patients 40-60 years without coronary atherosclerosis with widely varied HDL-C level were measured. The protein interactions were analyzed with STRING database. Read More

J Atheroscler Thromb 2020 10 6. Epub 2020 Oct 6.

Department of Cardiology, Rinku General Medical Center.

Aims: HDL particles have various anti-atherogenic functions, whereas HDL from atherosclerotic patients was demonstrated to be dysfunctional. One possible mechanism for the formation of dysfunctional HDL is the oxidation of its components. However, oxidized HDLs (Ox-HDLs) remain to be well investigated due to lack of reliable assay systems. Read More

Biochim Biophys Acta Mol Cell Biol Lipids 2020 03 19;1865(3):158592. Epub 2019 Dec 19.

Division BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Zuid-Holland, the Netherlands. Electronic address:

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters (CE) from high-density lipoproteins (HDL). An impaired SR-BI function leads to hyperalphalipoproteinemia with elevated levels of cholesterol transported in the HDL fraction. Accumulation of cholesterol in apolipoprotein B (apoB)-containing lipoproteins has been shown to alter skin lipid composition and barrier function in mice. Read More

Ann Hepatol 2019 Nov - Dec;18(6):879-882. Epub 2019 Aug 22.

Department of Endocrinology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico.

Introduction And Objectives: Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease that disrupts the cholesterol metabolism. Our aim was to investigate the frequency of dyslipidemias and to evaluate the risk of cardiovascular events in a historic cohort of patients with PBC.

Patients: All patients attended from 2000 to 2009 with histological diagnosis of PBC were included and were compared with healthy controls. Read More

Lab Med 2020 Mar;51(2):217-220

Centre for Applied Science, Belfast Metropolitan College, Belfast, Northern Ireland.

Hypercholesterolemia is characterized by serum cholesterol levels greater than 5 mmol per L. However, the distribution of cholesterol among lipoprotein classes has a significant bearing on diagnosis: high-low-density lipoprotein (LDL) cholesterol suggests familial hypercholesterolemia, whereas high-high-density lipoprotein (HDL) cholesterol is associated with hyperalphalipoproteinemia. On routine screening, a 23-year-old man presented with a total cholesterol level of 7. Read More

Atherosclerosis 2019 06 11;285:64-70. Epub 2019 Apr 11.

Department of Medical Sciences, Internal Medicine and CardioRespiratory Section, University of Ferrara, Ferrara, Italy. Electronic address:

Background And Aims: Epidemiological data showing that high-density lipoprotein cholesterol (HDL-C) is inversely associated with cardiovascular disease have led to the idea that cholesterol contained in this lipoprotein may be protective. Against, recent evidence suggests that the athero-protection from HDLs may result from other functions, unrelated to the carried cholesterol. HDL accessory proteins, such as paraoxonase 1 (PON1), have been suggested to endows HDL with antioxidant and anti-inflammatory properties and to contribute to the athero-protective function of the lipoprotein. Read More

J Clin Lipidol 2019 Mar - Apr;13(2):317-325. Epub 2019 Jan 11.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Community Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Cardiology, Rinku General Medical Center, Osaka, Japan. Electronic address:

Background: We previously reported that the patients with cholesteryl ester transfer protein (CETP) deficiency (CETP-D) show marked changes in the size and lipid compositions of high-density lipoprotein (HDL) and that they are not protected from atherosclerotic cardiovascular diseases, despite increased serum HDL-cholesterol (HDL-C) levels. HDL particles carry a variety of proteins, some of which are known to have antiatherogenic functions.

Objective: This study aimed to investigate the protein composition of HDL particles in patients with CETP-D. Read More

Curr Opin Lipidol 2019 04;30(2):56-62

Eurofins Genomics, Louisville, Kentucky, USA.

Purpose Of Review: To examine recent advances in our knowledge on the diagnosis of lipid disorders.

Recent Findings: Fasting values above the 99th percentile for direct LDL-cholesterol (LDL-C), lipoprotein(a), and triglycerides are greater than 225 mg/dl, greater than 160 mg/dl, and greater than 500 mg/dl (>5.82, >394, and >5. Read More

Lipids 2018 10 15;53(10):979-991. Epub 2018 Nov 15.

Institute of Molecular Genetics of the Russian Academy of Sciences, 2, Kurchatov Square, 123182, Moscow, Russia.

The heterogeneity and content of human plasma high-density lipoprotein (HDL) related to their atheroprotective properties determined by various molecular and cellular mechanisms still remain to be completely clarified. For 29 atherosclerosis-free male subjects, we studied the relationship of plasma lipid levels and the content of apolipoprotein A-I (apoA-I)-containing HDL with preβ-electrophoretic mobility, the efficiency of BODIPY-cholesterol efflux from RAW 264.7 macrophages to apolipoprotein B (apoB)-deficient plasma, and the expression level of 22 genes related to HDL metabolism in mononuclear cells. Read More

PLoS One 2018 5;13(1):e0190875. Epub 2018 Jan 5.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Objective: We previously reported that patients with cholesteryl ester transfer protein (CETP) deficiency (CETP-D) have a higher prevalence of atherosclerotic cardiovascular disease, in spite of increased HDL-C levels. However, characterization of HDL in CETP-D has not been well described. Therefore, we examined HDL particle number (PN) rather than HDL-C level. Read More

J Clin Lipidol 2018 Jan - Feb;12(1):110-115. Epub 2017 Nov 21.

Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine and the Veterans Affairs Medical Center, Baltimore, MD, USA. Electronic address:

Background: Hyperalphalipoproteinemia (HALP) is inversely correlated with coronary heart disease (CHD) although genetic variants associated with high serum levels of high-density lipoprotein cholesterol (HDL-C) have not been shown to be cardioprotective.

Objective: The objective of the study was to uncover novel genetic variants associated with HALP and possibly with reduced risk of CHD.

Methods: Exome sequencing data, HDL-C, and triglyceride levels were analyzed in 1645 subjects. Read More

J Clin Lipidol 2017 Sep - Oct;11(5):1192-1200.e3. Epub 2017 Jul 8.

Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Background: Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with risk of coronary artery disease (CAD) in epidemiologic studies. Despite this, the directionality of this relationship and the underlying biology behind it remain to be firmly established, especially at the extremes of HDL-C levels.

Objective: We investigated differences in the HDL phosphosphingolipidome in a rare population of subjects with premature CAD despite high HDL-C levels to gain insight into the association between the HDL lipidome and CAD disease status in this unusual phenotype. Read More

Arterioscler Thromb Vasc Biol 2017 06 20;37(6):1068-1075. Epub 2017 Apr 20.

From the Center for Advanced Models for Translational Sciences and Therapeutics, Department of Internal Medicine (J.Z., D.Y., J.L., J.X., Y.G., Y.F., T.Z., J.S., Y.K., M.G.-B., Y.E.C.), Department of Internal Medicine, Nephrology (A.V.M., S.P.), University of Michigan Medical Center, Ann Arbor; Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Japan (M.N., T.K., J.F.); Department of Pharmaceutical Sciences, Biointerfaces Institute, College of Pharmacy, University of Michigan (R.A., A.S.); and Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (L.L.).

Objective: CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial.

Approach And Results: We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents. Read More

Arterioscler Thromb Vasc Biol 2017 Mar 26;37(3):506-514. Epub 2017 Jan 26.

From the Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan (M.K., H.I., Y.Y.); Department of Medicine IV, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan (M.H.); and Department of Metabolism, Diabetes and Nephrology, Aizu Medical Center, Fukushima Medical University, Japan (K.T.).

Objective: Sphingosine-1-phosphate (S1P) is a vasoprotective lipid mediator. About two thirds of plasma S1P rides on high-density lipoprotein (HDL), and several pleiotropic properties of HDL have been ascribed to S1P. In human subjects, CETP (cholesteryl ester transfer protein) greatly influences HDL quantities. Read More

J Clin Lipidol 2016 Jul-Aug;10(4):898-904.e1. Epub 2016 Mar 21.

Centro de Pesquisa Clínica e Epidemiológica do Hospital Universitário, University of Sao Paulo Medical School, Sao Paulo, Brazil.

Background: There is evidence that extremely elevated high-density lipoprotein cholesterol (HDL-c), that is, hyperalphalipoproteinemia (HALP) may indicate dysfunctional HDL, conferring increased cardiovascular risk.

Objective: We studied carotid intima-media thickness (cIMT) a marker of subclinical vascular disease according to HDL-c distribution.

Methods: cIMT was studied in subjects with "normal" HDL-c levels (HDL-c 40-50 mg/dL for men; 50-60 mg/dL for women, mean 49. Read More

High Blood Press Cardiovasc Prev 2016 Mar 23;23(1):47-50. Epub 2016 Feb 23.

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

Introduction: There is existing debate as to the relationship between blood concentration of HDL (high density lipoprotein) and cardiovascular outcomes. Patients with hyperalphalipoproteinaemia (HALP) have high HDL levels and this can be attributed to a variety of factors.

Aim And Methods: This study aims for the first time to examine the HALP cohort and understand demographics, relationship with cardiovascular disease (CVD) risk and scoring with a cardiac risk calculator (QRISK 2 calculator). Read More

Nutrients 2015 Apr 2;7(4):2359-81. Epub 2015 Apr 2.

Nutritional Health Science Research Centre and Bioscience and Biotechnology, Chubu University, Kasugai 487-8501, Japan.

Despite its gradual increase in the past several decades, the prevalence of atherosclerotic vascular disease is low in Japan. This is largely attributed to difference in lifestyle, especially food and dietary habits, and it may be reflected in certain clinical parameters. Plasma high-density lipoprotein (HDL) levels, a strong counter risk for atherosclerosis, are indeed high among the Japanese. Read More

Mol Cells 2014 Nov 6;37(11):777-84. Epub 2014 Nov 6.

Laboratory Science, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.

Epidemiologic studies have shown that low-density lipoprotein cholesterol (LDL-C) is a strong risk factor, whilst high-density lipoprotein cholesterol (HDL-C) reduces the risk of coronary heart disease (CHD). Therefore, strategies to manage dyslipidemia in an effort to prevent or treat CHD have primarily attempted at decreasing LDL-C and raising HDL-C levels. Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester for triglycerides between HDL and VLDL and LDL. Read More

Nutr Metab Cardiovasc Dis 2014 Jul 1;24(7):777-83. Epub 2014 Mar 1.

Department of Pharmacy, University of Parma, Parma, Italy.

Background And Aims: The relationships between very high plasma HDLc and subclinical atherosclerosis are still a matter of debate.

Methods And Results: Twenty subjects with primary hyperalphalipoproteinemia (HAL, with HDLc in the highest 10th percentile and absence of overt secondary causes of this condition), aged 30-65 years, were compared with 20 age and sex-matched controls. Lipid determination, lipoprotein particle distribution (Lipoprint(®)), Cholesterol Efflux Capacity (CEC), plasma adhesion molecule, analyses of CETP, SRB1 and LIPG genes and of different markers of subclinical vascular disease (ankle-brachial index, ABI; carotid intima-media thickness, cIMT; brachial-artery flow mediated dilation, FMD) were performed. Read More

Biochim Biophys Acta 2014 Apr 3;1841(4):495-504. Epub 2014 Jan 3.

Nutritional Health Science Research Center, Chubu University, Matsumoto-cho 1200, Kasugai 487-8501, Japan. Electronic address:

Cholesteryl ester transfer protein (CETP)-deficiency manifests a unique plasma lipoprotein profile without other apparent symptoms. It is highly common in East Asia while rather rare anywhere else. A potential environmental screening factor(s) may therefore contribute to this eccentric distribution, such as its selective advantage against a regional illness, most likely an infectious disease, in relation to plasma lipoproteins. Read More

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

Clin Genet 2014 May 24;85(5):433-40. Epub 2013 Jun 24.

Department of Vascular Medicine.

Apolipoprotein C3 (APOC3) mutations carriers typically display high plasma high-density lipoprotein cholesterol (HDL-C) and low triglycerides (TGs). We set out to investigate the prevalence and clinical consequences of APOC3 mutations in individuals with hyperalphalipoproteinemia. Two novel mutations (c. Read More

Clin Chim Acta 2013 Feb 5;416:92-5. Epub 2012 Dec 5.

Hormonal and Metabolic Disorders Research Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Patumwan, Bangkok 10330, Thailand.

Background: Variants in the CETP and the LIPC genes, encoding cholesteryl ester transfer protein and hepatic lipase, respectively, are associated with high levels of HDL-cholesterol or hyperalphalipoproteinemia (HALP). Recently, we have identified three novel variants in the CETP promoter and two novel variants in LIPC in Thai subjects with HALP. In this study, we investigated the functions of these 5 variants in vitro. Read More

FASEB J 2013 Mar 29;27(3):1236-44. Epub 2012 Nov 29.

Nutritional Health Science Research Centre and Food and Nutritional Sciences, Chubu University, Kasugai 487-8501, Japan.

Familial cholesteryl ester transfer protein (CETP) deficiency is more common in some East Asian populations than elsewhere, suggesting the possibility of a selective advantage of this genetic defect against regional infectious diseases. Historically, infection with the Asian blood fluke Schistosoma japonicum has been endemic in these regions, including Japan. We previously reported that eggs of S. Read More

PLoS One 2012 27;7(8):e37437. Epub 2012 Aug 27.

Xenon Pharmaceuticals Inc., Burnaby, Canada.

To date, few mutations are described to underlie highly-elevated HDLc levels in families. Here we sequenced the coding regions and adjacent sequence of the LIPG, CETP, and GALNT2 genes in 171 unrelated Dutch Caucasian probands with HDLc≥90th percentile and analyzed segregation of mutations with lipid phenotypes in family members. In these probands, mutations were most frequent in LIPG (12. Read More

Am J Cardiol 2012 Jul 29;110(1):62-6. Epub 2012 Mar 29.

Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

Genetic factors associated with hyperalphalipoproteinemia (HALP; or high levels of high-density lipoprotein cholesterol) are incompletely understood. The aim of this study was to resequence 3 candidate genes, CETP, LIPC, and LIPG, which encode cholesteryl ester transfer protein, hepatic lipase, and endothelial lipase, respectively, in Thai subjects with HALP and compare them to normolipidemic controls. Sequence variants of CETP, LIPC, and LIPG were identified by sequencing exons and exon-intron junctions in 64 subjects with high-density lipoprotein cholesterol levels ≥2. Read More

Curr Vasc Pharmacol 2012 Jul;10(4):422-31

Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., Metabolic DBA, Grenzacherstrasse 124, Basel, Switzerland.

Hyperalphalipoproteinemia, as observed in patients who are either homozygous or heterozygous for cholesteryl ester transfer protein (CETP) deficiency, has been shown to be associated with striking changes in apolipoprotein size distribution, namely, of high-density lipoprotein (HDL) and HDL-like particles. We compared the effect of varying degrees of CETP activity on the HDL apolipoprotein profile in Caucasian CETP-deficient subjects and following pharmacological decrease in CETP activity, using Size Exclusion Chromatography followed by Reverse Phase Protein Array (SEC RPA). The main HDL-associated apolipoproteins (Apo), i. Read More

Int J Cardiovasc Imaging 2010 Jan 30;26(1):27-34. Epub 2009 Oct 30.

Clinical Pathology Department, Medical School, University of Campinas, Campinas, SP, Brazil.

To determine whether hyperalphalipoproteinemia modifies carotid intima-media thickness (cIMT) and/or influences the relationship of clinical and biochemical parameters with cIMT. This study was conducted on 169 asymptomatic individuals, classified as hyperalphalipoproteinemic (Hyper-A) (Hyper-A, n = 71, HDL-C > or =68 mg/dL) and controls (CTL) (CTL, n = 98, HDL-C >32 and <68 mg/dL). Enzymatic, nephelometric and ultracentrifugation methods were used for biochemical determinations. Read More