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J Clin Lipidol 2019 Jan 11. 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

Lipids 2018 Oct 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

Clin Chim Acta 2009 Aug 19;406(1-2):52-6. Epub 2009 May 19.

Division of Metabolism, Chiba Children's Hospital, Chiba 266-0007, Japan.

Background: Hyperalphalipoproteinemia is associated with cholesteryl ester transfer protein (CETP) deficiency in adults but has unclear associations in children.

Methods: We measured lipoproteins in 19 heterozygotes (D442G, n=17; I14A, n=2), one D442G/I14A compound heterozygote, 13 non-affected siblings, and 30 healthy controls at birth, 3-4 months, and 12 months.

Results: CETP mass was 32-70% lower in heterozygotes than in controls throughout the year. Read More

Metabolism 2009 Aug 18;58(8):1178-84. Epub 2009 Jun 18.

Biomedical Sciences Program, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.

Previous studies have shown that CETP and LIPC mutations contribute to hyperalphalipoproteinemia (HALP) in some populations. We investigated whether activities in cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) contribute to HALP in the Thai population and performed genetic analyses of the CETP and LIPC genes. We recruited 38 individuals with high-density lipoprotein cholesterol (HDL-C) levels of at least 2. Read More

J Clin Endocrinol Metab 2009 Apr 21;94(4):1451-7. Epub 2009 Jan 21.

Department of Medicine, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.

Context: In mice, scavenger receptor class B, type I (SR-BI) receptor protein deficiency is associated with elevated high-density lipoprotein (HDL)-cholesterol (HDL-C) levels.

Objective: Our objective was to determine the relationship between SR-BI protein and HDL-C levels in humans.

Design: This was a prospective study of adults with hyperalphalipoproteinemia. Read More

Exp Gerontol 2009 Mar 17;44(3):136-60. Epub 2008 Nov 17.

Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.

High-density lipoprotein (HDL) particles exhibit multiple antiatherogenic effects. They are key players in the reverse cholesterol transport which shuttles cholesterol from peripheral cells (e.g. Read More

Metabolism 2008 Dec;57(12):1719-24

Department of Physiological Nursing, University of California San Francisco, San Francisco, CA 94143, USA.

We previously demonstrated the role of a phospholipid transfer protein (PLTP) gene variation (rs2294213) in determining levels of high-density lipoprotein cholesterol (HDL-C) in hypoalphalipoproteinemia (HypoA). We have now explored the role of PLTP in hyperalphalipoproteinemia (HyperA). The human PLTP gene was screened for sequence anomalies by DNA melting in 107 subjects with HyperA. Read More

Clin Chim Acta 2008 Sep 15;395(1-2):62-7. Epub 2008 May 15.

Tokyo Medical and Dental University, Ichikawa, Japan.

Background: The main purpose of this study was to evaluate an HPLC method for LDL-cholesterol determination in the presence of abnormal lipoproteins.

Methods: We compared LDL-cholesterol levels obtained by HPLC (HPLC-LDL), Friedewald (F-LDL), and beta-quantification (BQ-LDL) methods on 47 healthy volunteers and 50 outpatients with lipid disorders, including apolipoprotein E2/2 phenotype, cholesteryl ester transfer protein deficiency and lipoprotein lipase deficiency.

Results: For the control group (n=50), the HPLC-LDL and the F-LDL correlated highly with the BQ-LDL (r=0. Read More

Biol Pharm Bull 2008 Mar;31(3):340-7

Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.

We examined the correlations between serum dolichol levels and laboratory test parameters in patients affected by disease, as well as the distribution of dolichol in sera from patients with hyperbetalipoproteinemia and hyperalphalipoproteinemia. Serum dolichol was evaluated by a reverse-phase HPLC method. After centrifugation, the serum dolichol found in healthy controls was mainly associated with medium-sized particles of the high-density lipoprotein (HDL) fraction. Read More

J Hum Genet 2008 27;53(3):193-200. Epub 2007 Dec 27.

Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, Japan.

Hepatic lipase (HL) plays a major role in the regulation of plasma lipids. Several groups seeking to find association between the gene encoding HL (LIPC) and plasma concentrations of high-density lipoprotein cholesterol (HDLc) using various methods and populations have reported conflicting results. We have approached the problem of demonstrating a relationship between the LIPC locus and HDLc by means of haplotype association using four single nucleotide polymorphisms (SNPs) (rs12594375G/A, rs8023503C/T, rs4775047C/T, and rs11634134T/A) located in intron 1 of the LIPC gene in two independent Japanese populations consisting of 2,970 and 1,638 individuals, respectively. Read More

J Lipid Res 2007 Mar 27;48(3):674-82. Epub 2006 Dec 27.

Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.

It is unclear whether cholesteryl ester transfer protein (CETP) contributes to high density lipoprotein cholesterol (HDL-C) levels in hyperalphalipoproteinemia (HALP) in Caucasians. Moreover, even less is known about the effects of hereditary CETP deficiency in non-Japanese. We studied 95 unrelated Caucasian individuals with HALP. Read More

J Mol Med (Berl) 2006 Aug 20;84(8):647-50. Epub 2006 Jul 20.

University of Maryland and Veterans Affairs Medical Center, Baltimore, MD, USA.

High levels of high-density lipoprotein cholesterol (HDL-C) occur with cholesteryl ester transfer protein (CETP) deficiency. However, the extent to which CETP deficiency states may be associated with protection against coronary artery disease (CAD) has been controversial. We evaluated a Greek pedigree with high levels of HDL-C and no history of premature CAD. Read More

Circ J 2005 May;69(5):609-12

Second Department of Internal Medicine, Iwate Medical University School of Medicine, Japan.

A 54-year-old female was admitted to hospital complaining of oppressive anterior chest pain during exercise. Treadmill exercise ECG testing showed significant ischemic ECG changes, and electron-beam computed tomography demonstrated patchy calcifications in the coronary artery. Coronary angiography revealed a significant stenotic lesion of the right coronary artery. Read More

Rev Med Chil 2004 Apr;132(4):421-8

Departamento de Nutrición, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.

Background: High density lipoprotein (HDL) cholesterol is inversely associated to atherosclerotic cardiovascular risk. Disturbances in HDL cholesterol plasma levels are frequent in the Chilean population, however the pathophysiological mechanisms are unknown.

Aim: To evaluate the mechanisms involved in the hypo and hyper alfalipoproteinemias in Chilean subjects. Read More

J Atheroscler Thromb 2004 ;11(3):110-21

Department of Advanced Technology and Development, BML, Inc., Saitama, Japan.

Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins. Since CETP regulates the plasma levels of HDL cholesterol and the size of HDL particles, CETP is considered to be a key protein in reverse cholesterol transport (RCT), a protective system against atherosclerosis. The importance of plasma CETP in lipoprotein metabolism was demonstrated by the discovery of CETP-deficient subjects with marked hyperalphalipoproteinemia (HALP). Read More

Arterioscler Thromb Vasc Biol 2004 Mar 22;24(3):526-33. Epub 2004 Jan 22.

Dyslipoproteinemia and Atherosclerosis Research Unit (U.551),National Institute for Health and Medical Research, Hôpital de la Pitié, Paris, France.

Objective: Hyperalphalipoproteinemia (HALP) is characterized by elevated plasma levels of high-density lipoprotein (HDL) particles with altered composition, metabolism, and function. The impact of such modification on antioxidative activities of HDL subfractions is indeterminate.

Methods And Results: Gradient fractionation revealed that buoyant HDL2b and 2a and small dense HDL3b and 3c levels were elevated up to 2. Read More

J Lipid Res 2004 Mar 1;45(3):448-55. Epub 2003 Dec 1.

Lipid Metabolism Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.

Our purpose was to compare HDL subpopulations, as determined by nondenaturing two-dimensional gel electrophoresis followed by immunoblotting for apolipoprotein A-I (apoA-I), apoA-II, apoA-IV, apoCs, and apoE in heterozygous, compound heterozygous, and homozygous subjects for cholesteryl ester transfer protein (CETP) deficiency and controls. Heterozygotes, compound heterozygotes, and homozygotes had CETP masses that were 30, 63, and more than 90% lower and HDL-cholesterol values that were 64, 168, and 203% higher than those in controls, respectively. Heterozygotes had approximately 50% lower pre-beta-1 and more than 2-fold higher levels of alpha-1 and pre-alpha-1 particles than controls. Read More

Atherosclerosis 2003 Nov;171(1):131-6

Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Probucol, an antioxidative and hypolipidemic agent, has been postulated to increase reverse cholesterol transport by enhancing cholesteryl ester transfer protein (CETP) activity. However, its clinical implication in CETP deficient patients has not been fully defined. To characterize the effects of probucol in the absence of CETP, we evaluated the changes in lipid profile, lipid peroxidation, and paraoxonase 1 (PON1) activity in two complete CETP deficient patients, caused by treatment with probucol. Read More

Metabolism 2003 Apr;52(4):432-6

Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Italy.

Hypoalphalipoproteinemia (Hypo-A), a lipid disorder characterized by low high-density lipoprotein (HDL)-cholesterol (HDL-C) levels, is frequently associated with an increased risk of suffering future coronary heart disease (CHD). Conversely, hyperalphalipoproteinemia (Hyper-A) is a characterized by high HDL-C concentrations and is possibly associated with longevity and protection against CHD. Whether plasma C-reactive protein (CRP) level, an emerging marker of CHD risk, may be influenced by either extremely low or high HDL-C concentrations is yet to be determined. Read More

Circulation 2003 Mar;107(10):1366-71

Department of Cardiovascular Genetics, McGill University Health Centre, Montréal, Canada.

Background: Prospective studies have examined the relationship between coronary artery disease and low plasma levels of high-density lipoprotein cholesterol (HDL-C).

Methods And Results: We investigated the causes of hypoalphalipoproteinemia (HypoA; HDL-C <5th percentile) in 64 subjects (12 women and 52 men). Apolipoprotein AI-mediated cellular cholesterol and phospholipid efflux were measured in fibroblasts from HypoA subjects, 9 controls, 2 patients with Tangier disease, and 5 patients with hyperalphalipoproteinemia. Read More

Atherosclerosis 2003 Jan;166(1):177-85

Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, B5, Suita, Osaka 565-0871, Japan.

A patient with cholesteryl ester transfer protein (CETP) deficiency presents with marked hyperalphalipoproteinemia (HALP). To investigate the contribution of CETP deficiency to the cause of HALP (HDL-C> or =1.94 mmol/l, 75 mg/dl), we investigated the CETP activities and the prevalence of genetic CETP mutations among 624 Japanese HALP subjects. Read More

J Lipid Res 2002 Jul;43(7):1011-8

Research Department, R&D Center, BML, 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan.

Cholesteryl ester transfer protein (CETP) deficiency is one of the most important and common causes of hyperalphalipoproteinemia (HALP) in the Japanese. CETP deficiency is thought to be a state of impaired reverse cholesterol transport, which may possibly lead to the development of atherosclerotic cardiovascular disease despite high HDL-cholesterol (HDL-C) levels. Thus, it is important to investigate whether HALP is caused by CETP deficiency. Read More

Arterioscler Thromb Vasc Biol 2002 Feb;22(2):317-22

Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milan, Italy.

The plasma concentration of high-density lipoprotein cholesterol (HDL-C) is inversely correlated with the incidence of atherosclerotic vascular events. In the present study, we evaluated pre-intrusive atherosclerosis in subjects with plasma HDL-C at the extremities of normal distribution. Fifty-five subjects with primary hypoalphalipoproteinemia (HypoALP) or hyperalphalipoproteinemia (HyperALP) were compared with fifty-five control subjects with average HDL-C levels, matched for sex, age, and plasma cholesterol. Read More

Front Biosci 2001 Mar 1;6:D366-87. Epub 2001 Mar 1.

Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

Plasma lipid transfer proteins include plasma cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP). Plasma CETP facilitates the transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to apolipoprotein (apo) B-containing lipoproteins, and is a key protein in reverse cholesterol transport which protects vessel walls from atherosclerosis. The importance of plasma CETP in lipoprotein metabolism was highlighted by the discovery of CETP-deficient subjects with a marked hyperalphalipoproteinemia (HALP). Read More

Biochim Biophys Acta 2000 Dec;1529(1-3):257-75

Department of Internal Medicine and Molecular Science, Graduate School of Medicine, B5, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan.

Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins. Since CETP regulates the plasma levels of HDL cholesterol and the size of HDL particles, CETP is considered to be a key protein in reverse cholesterol transport, a protective system against atherosclerosis. CETP, as well as plasma phospholipid transfer protein, belongs to members of the lipid transfer/lipopolysaccharide-binding protein (LBP) gene family, which also includes the lipopolysaccharide-binding protein (LBP) and bactericidal/permeability-increasing protein. Read More

Clin Chim Acta 2000 Nov;301(1-2):103-17

Department of Clinical Chemistry, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.

We investigated the detailed distribution of high-density lipoproteins (HDL) particle size in patients with cholesteryl ester transfer protein (CETP) deficiency. Serum samples pre-stained with Sudan black B were electrophoresed using 4-30% polyacrylamide gradient gels, and the Stokes diameter of HDL particles was determined in 23 patients with genetic CETP deficiency, nine patients with hyperalphalipoproteinemia and seven subjects with normal HDL cholesterol concentrations. The mean Stokes diameter of HDL particles in CETP deficient patients (11. Read More

Atherosclerosis 2000 Oct;152(2):271-85

Department of Internal Medicine and Molecular Science, Graduate School of Medicine, B5, Osaka University, 2-2 Yamada-oka, Suita, 565-0871, Osaka, Japan.

Hyperalphalipoproteinemia (HALP) is caused by a variety of genetic and environmental factors. Among these, plasma cholesteryl ester transfer protein (CETP) deficiency is the most important and frequent cause of HALP in the Asian populations. CETP facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein (apo) B-containing lipoproteins, and is a key protein in the reverse cholesterol transport system. Read More

Exp Gerontol 1999 Jul;34(4):539-48

Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and College of Basic Medicine, Peking Union Medical College, Beijing, China.

Serum high-density lipoprotein level is known to be correlated inversely with the incidence and mortality rates of ischemic heart disease. Although some reports pointed out that in case of hyperalphalipoproteinemia, lesions in the coronary arteries were occasionally found, it is also noticed that in very rare condition, no atheromatous lesions found even in patients with hereditary alphalipoprotein deficiency (Funke et al., 1991). Read More

Life Sci 2000 Mar;66(18):1683-94

Department of Molecular Biology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert, Ann Arbor, MI 48105, USA.

Past studies have shown that a high saturated fatty acid diet containing coconut oil elevates plasma HDL cholesterol and apolipoprotein A-I (apoA-1) in rabbits through a mechanism involving increased synthesis. We have extended those studies by investigating expression of the hepatic apolipoprotein A-I gene and other lipid related genes in that model. Rabbits fed a diet containing 14% coconut oil for 4 weeks showed HDL-C elevations of 170% to 250% over chow-fed controls with peak differences occurring at 1 week. Read More

Arterioscler Thromb Vasc Biol 2000 Feb;20(2):459-66

Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.

High density lipoprotein (HDL) metabolism and lecithin:cholesterol acyltransferase (LCAT)-induced HDL remodeling were investigated in transgenic mice expressing human apolipoprotein (apo) AI or an apoAI/apoAII chimera in which the Arg123-Tyr166 domain of apoAI was substituted with the Ser12-Ala75 domain of apoAII. Expression of apoAI and of the apoAI/apoAII chimera resulted in a respective 3. 5-fold and 2. Read More