Low Density Lipoprotein Subfractions: Systematic Review of Measurement Methods and Association with Cardiovascular Outcomes

Total Page:16

File Type:pdf, Size:1020Kb

Low Density Lipoprotein Subfractions: Systematic Review of Measurement Methods and Association with Cardiovascular Outcomes Technology Assessment Low Density Lipoprotein Subfractions: Systematic Review of Measurement Methods and Association with Cardiovascular Outcomes Technology Assessment Program June 16, 2008 Agency for Healthcare Research and Quality 540 Gaither Road Rockville, Maryland 20850 1 Low Density Lipoprotein Subfractions: Systematic Review of Measurement Methods and Association with Cardiovascular Outcomes Technology Assessment Report Project ID: LIPS0707 June 16, 2008 Tufts Evidence­based Practice Center Ethan Balk, MD MPH Stanley Ip, MD Mei Chung, MPH Joseph Lau, MD Alice H. Lichtenstein, DSc This report is based on research conducted by the Tufts Evidence­based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290­02­0022). The findings and conclusions in this document are those of the authors who are responsible for its contents. The findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of the Agency for Healthcare Research and Quality or of the U.S. Department of Health and Human Services. The information in this report is intended to help health care decision­makers; patients and clinicians, health system leaders, and policymakers, make well­informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, ie, in the context of available resources and circumstances presented by individual patients. This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied. None of the investigators has any affiliations or financial involvement related to the material presented in this report. 2 Table of contents Abbreviations......................................................................................................................................................... 5 CHAPTER 1. INTRODUCTION........................................................................................................................... 7 Key questions to be addressed.......................................................................................................................... 8 CHapter 2. methods............................................................................................................................................. 10 Search strategy .............................................................................................................................................. 10 Classification of LDL Subfraction Methods (Tests)........................................................................................ 10 Study Selection.............................................................................................................................................. 11 Data Extraction.............................................................................................................................................. 13 Quality Assessment ....................................................................................................................................... 14 Applicability assessment................................................................................................................................ 14 Summary Tables............................................................................................................................................ 15 CHapter 3. Results............................................................................................................................................... 17 Literature Search ........................................................................................................................................... 17 Question 1 .................................................................................................................................................... 17 Question 2 .................................................................................................................................................... 21 Question 3 .................................................................................................................................................... 25 Question 3.1 ........................................................................................................................................... 25 Question 3.2 ........................................................................................................................................... 25 Question 4 .................................................................................................................................................... 32 Question 4.1 ........................................................................................................................................... 32 Question 4.2 ........................................................................................................................................... 63 Question 4.3 ........................................................................................................................................... 63 Question 4.4 ........................................................................................................................................... 73 CHapter 4. discussion .......................................................................................................................................... 80 LDL subfraction methodology ................................................................................................................ 80 Association between LDL subfractions and CVD.................................................................................... 81 Limitations ............................................................................................................................................. 83 Future research ....................................................................................................................................... 84 Summary................................................................................................................................................ 86 References ........................................................................................................................................................... 87 Appendix A. Search strategy................................................................................................................................ 94 Appendix B. Rejected articles.............................................................................................................................. 95 Appendix C. Potential treatment studies ............................................................................................................ 104 3 Tables and Figures Table 1. Comparison of different methods for measuring LDL subfractions ......................................................... 23 Table 2. Test Variability (or Imprecision) ........................................................................................................... 30 Table 3a. Characteristics of the nested case­control studies of incident CVD and NMR­measured LDL subfractions .............................................................................................................................. 36 Table 3b. Nested case­control studies of incident CVD and NMR­measured LDL subfractions ............................ 37 Table 4. Longitudinal study of NMR­measured LDL subfractions and progression of CVD ................................. 39 Table 5a. Characteristics of patients in the cross­sectional studies of prevalent CVD and NMR­measured LDL subfractions .............................................................................................................................. 40 Table 5b. Cross­sectional studies of NMR­measured LDL subfractions and prevalent CVD outcomes 41 Table 6a. Characteristics of case­control studies of prevalent CVD and LipoPrint GE­measured LDL subfractions 42 Table 6b. Case­control studies of LipoPrint GE­measured LDL subfractions and prevalent CVD .......................... 42 Table 7a. Characteristics of patients in the cross­sectional studies of prevalent CVD and LipoPrint GE­measured LDL subfractions ............................................................................................................................... 43 Table 7b. Cross­sectional studies of LipoPrint GE­measured LDL subfractions and prevalent CVD ...................... 44 Table 8. Longitudinal study of time­averaged Berkeley HeartLab GE­measured LDL subfractions and progression of CVD..................................................................................................................................... 45 Table 9. Association between LDL Subfraction and incident CVD events (not full extraction).............................. 49 Table 10. Association between LDL Subfraction
Recommended publications
  • An Educational Booklet for Patients with Familial Hypercholesterolemia
    Illustrations > Jean Lambert Illustrations graphic design > www.mine-de-rien.net graphic Chol/29/P030/01-01/10 NLA An educational booklet for patients with familial hypercholesterolemia This brochure was provided by Genzyme Corporation for use by the Foundation of the National Lipid Association. DR. LEIV OSE www.learnyourlipids.com CONTENTS PART 1 What will you learn from this booklet? 02 FAMILIAL HYPERCHOLESTEROLEMIA PART 1: FAMILIAL HYPERCHOLESTEROLEMIA 03 1 - What is Familial Hypercholesterolemia? 03 WHAT WILL YOU 2 - What is LDL-Cholesterol? 04 3 - What are the causes of FH? 05 LEARN FROM THIS GREAT GRANDMOTHER GREAT GRANDFATHER 4 - When should FH be suspected? 07 FH NON FH BOOKLET? 5 - How is FH diagnosed? 09 6 - How early can FH be diagnosed? 09 Woman You will learn about Familial PART 2: TREATMENT 10 GRANDMOTHER GRANDFATHER Hypercholesterolemia, NON FH FH Woman with FH 1 - How can LDL-Cholesterol be reduced? 10 its cause, and the potential 2 - Step 1: Dietary management of FH 11 Man consequences of this a) How does diet affect LDL-Cholesterol? 11 disease. You will learn b) What sort of diet? 11 Man with FH about high cholesterol 3 - Step 2: Using medication 12 AUNT MOTHER FATHER UNCLE and what this might mean a) How does medication affect LDL-Cholesterol? 12 NON FH FH NON FH FH for your heart and blood b) Which drug treatments reduce LDL-Cholesterol and how? 13 FIGURE 1: 4 - Why is lifelong treatment important? vessels. Most importantly 15 FH is an inherited disease, you will learn how to find PART 3: CARDIOVASCULAR DISEASE AND LIPOPROTEINS 16 which can usually be traced out whether someone in 1 - What is cardiovascular disease? 16 DAUGTER SON over several generations.
    [Show full text]
  • Core Laboratory
    Performance of the vast majority of Hematology, Coagulation, Urinalysis, Clinical Chemistry and Toxicology testing procedures is conducted in the CORE LABORATORY - an advanced, highly automated area where whole blood, serum, plasma, urine and other biological fluid specimens are tested for a comprehensive menu of state-of-the-art laboratory procedures. Significant testing procedures for Clinical Chemistry and Toxicology includes panels currently approved by the Centers for Medicare and Medicaid Services: Basic Metabolic Panel; Comprehensive Metabolic Panel; Liver Function Panel; Renal Function Panel; and Electrolyte Panel. Other key tests include the Lipid Profile (Cholesterol, Triglyceride, HDL- Cholesterol and LDL-Cholesterol), major markers of cardiovascular disease and risk [such as Troponin I, Myoglobin and Beta-type natriuretic peptide (commonly referred to as BNAT or BNP)], critical care analytes, beta-HCG, and significant therapeutic drug levels. Urinary toxicology screens for major drugs of abuse (and/or key metabolites) are also performed. The cornerstones of Hematology testing are analyses of the complete blood count (CBC) and the differential (DIFF). These include evaluation of: (1) white blood cell count and differential with percentage and absolute value given for the leukocyte components; (2) circulating erythrocytes by means of hemoglobin, hematocrit, red blood cell count, and red blood cell indices; and (3) measurement of platelet concentration by count and/or estimation. Morphological variations and changes of cellular constituents are reported. Alteration of any aspect of the hemostatic mechanism may cause abnormal bleeding in a wide variety of familial and acquired disorders. These defects may be differentiated by a profile of significant Coagulation laboratory tests that includes PT, PTT, Fibrinogen, FDP, and D-Dimer for monitoring anticoagulant therapy.
    [Show full text]
  • Genetic Testing for Familial Hypercholesterolemia AHS – M2137
    Corporate Medical Policy Genetic Testing for Familial Hypercholesterolemia AHS – M2137 File Name: genetic_testing_for_familial_hypercholesterolemia Origination: 01/01/2019 Last CAP Review: 07/2021 Next CAP Review: 07/2022 Last Review: 07/2021 Description of Procedure or Service Definitions Familial hypercholesterolemia (FH) is a genetic condition that results in premature atherosclerotic cardiovascular disease due to lifelong exposure to elevated low-density lipoprotein cholesterol (LDL-C) levels (Sturm et al., 2018). FH encompasses multiple clinical phenotypes associated with distinct molecular etiologies. The most common is an autosomal dominant disorder caused by mutations in one of three genes, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), and proprotein convertase subtilisin-like kexin type 9 (PCSK9) (Ahmad et al., 2016; Goldberg et al., 2011). Rare autosomal recessive disease results from mutation in low-density lipoprotein receptor adaptor protein (LDLRAP) (Garcia et al., 2001). Related Policies Cardiovascular Disease Risk Assessment AHS – G2050 ***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician. Policy BCBSNC will provide coverage for genetic testing for familial hypercholesterolemia when it is determined the medical criteria or reimbursement guidelines below are met. Benefits Application This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore member benefit language should be reviewed before applying the terms of this medical policy. When Genetic Testing for Familial Hypercholesterolemia is covered 1. Genetic testing to establish a molecular diagnosis of Familial Hypercholesterolemia is considered medically necessary when BOTH of the following criteria are met: A.
    [Show full text]
  • Lrp1 Modulators
    Last updated on February 14, 2021 Cognitive Vitality Reports® are reports written by neuroscientists at the Alzheimer’s Drug Discovery Foundation (ADDF). These scientific reports include analysis of drugs, drugs-in- development, drug targets, supplements, nutraceuticals, food/drink, non-pharmacologic interventions, and risk factors. Neuroscientists evaluate the potential benefit (or harm) for brain health, as well as for age-related health concerns that can affect brain health (e.g., cardiovascular diseases, cancers, diabetes/metabolic syndrome). In addition, these reports include evaluation of safety data, from clinical trials if available, and from preclinical models. Lrp1 Modulators Evidence Summary Lrp1 has a variety of essential functions, mediated by a diverse array of ligands. Therapeutics will need to target specific interactions. Neuroprotective Benefit: Lrp1-mediated interactions promote Aβ clearance, Aβ generation, tau propagation, brain glucose utilization, and brain lipid homeostasis. The therapeutic effect will depend on the interaction targeted. Aging and related health concerns: Lrp1 plays mixed roles in cardiovascular diseases and cancer, dependent on context. Lrp1 is dysregulated in metabolic disease, which may contribute to insulin resistance. Safety: Broad-spectrum Lrp1 modulators are untenable therapeutics due to the high potential for extensive side effects. Therapies that target a specific Lrp1-ligand interaction are expected to have a better therapeutic profile. 1 Last updated on February 14, 2021 Availability: Research use Dose: N/A Chemical formula: N/A S16 is in clinical trials MW: N/A Half life: N/A BBB: Angiopep is a peptide that facilitates BBB penetrance by interacting with Lrp1 Clinical trials: S16, an Lrp1 Observational studies: sLrp1 levels are agonist was tested in healthy altered in Alzheimer’s disease, volunteers (n=10) in a Phase 1 cardiovascular disease, and metabolic study.
    [Show full text]
  • Inflammatory Mechanisms Affecting the Lipid Profile in Patients with Systemic Lupus Erythematosus CECILIA P
    Inflammatory Mechanisms Affecting the Lipid Profile in Patients with Systemic Lupus Erythematosus CECILIA P. CHUNG, ANNETTE OESER, JOSEPH SOLUS, INGRID AVALOS, TEBEB GEBRETSADIK, AYUMI SHINTANI, MacRAE F. LINTON, SERGIO FAZIO, and C. MICHAEL STEIN ABSTRACT. Objective. Increased low density lipoprotein (LDL) cholesterol and triglycerides, and decreased high density lipoprotein (HDL) cholesterol concentrations are associated with adverse cardiovascular risk in the general population. Patients with systemic lupus erythematosus (SLE) have an altered lipid profile characterized by increased triglycerides and decreased HDL cholesterol concentrations. We examined the relationships between lipid concentrations, cytokines, and inflammatory markers in patients with SLE. Methods. Fasting lipid concentrations, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured in 110 patients with SLE. Disease activity was quantified by the SLE Disease Activity Index (SLEDAI), and disease damage by the Systemic Lupus International Collaborating Clinics (SLICC) score. Concentrations of circulating tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and insulin were measured and insulin sensitivity calculated. Results. Lower concentrations of HDL cholesterol were independently associated with higher ESR (p < 0.001), IL-6 (p = 0.02), SLEDAI (p = 0.04), and TNF-α (p = 0.04) after adjustment for age, sex, race, body mass index, insulin sensitivity, and current use of corticosteroids or hydroxychloroquine. Triglyceride concentrations were
    [Show full text]
  • Lipid Profile and Its Relationship with Blood
    Onkar Singh et al. Lipid profile and blood glucose levels in MetS National Journal of Physiology, DOI: 10.5455/njppp.2015.5.051120141 NJPPP Pharmacy & Pharmacology http://www.njppp.com/ RESEARCH ARTICLE Correspondence LIPID PROFILE AND ITS RELATIONSHIP Onkar Singh ([email protected]) WITH BLOOD GLUCOSE LEVELS IN Received 27.08.2014 METABOLIC SYNDROME Accepted 09.09.2014 1 1 2 Onkar Singh , Mrityunjay Gupta , Vijay Khajuria Key Words Metabolic Syndrome; 1 Department of Physiology, Government Medical College, Jammu, India Dyslipidemia; Lipid Pattern; 2 Department of Pharmacology, Government Medical College, Jammu, India Type 2 Diabetes Mellitus Background: Metabolic syndrome (MetS) and its associated factors such as dyslipidemia and hyperglycemia are associated with increased risk of cardiovascular disease (CVD). Aims and Objective: To assess lipid profile and its relation with blood glucose levels in patients with MetS. Materials and Methods: This cross-sectional study included 72 male patients with MetS. Anthropometry, lipid profile, blood glucose, and presence of MetS (JIS criteria) were determined. Results: High triglyceride (TG) level (>200 mg/dL, 44.4%) was the most common dyslipidemia followed by low levels of high-density lipoprotein cholesterol (<40 mg/dL, 19.4%). High total cholesterol levels (>240 mg/dL, 13.8%) and high low- density lipoprotein cholesterol levels (>160 mg/dL, 9.7%) were observed. On comparison, no significant differences in lipid levels of MetS patients with normal fasting glucose, impaired fasting glucose, and type 2 diabetes mellitus were observed. Conclusions: Dyslipidemia was frequent in patients with MetS. High TG was the most common lipid abnormality, and a large number of patients had more than one abnormal lipid parameter.
    [Show full text]
  • Community Lab Costs
    Sickle Cell This tests for the genetic trait which may lead to sickle cell anemia. Osteoporosis Screening This uses ultrasound to screen people for low bone density or osteoporosis and is completed by painlessly scanning the heel. Because osteoporosis rarely causes signs or symptoms until it’s advanced, the National Osteoporosis Foundation recommends a bone density test if you are: • A woman older than age 65 or a man older than age 70 • A postmenopausal woman with at least one risk factor for osteoporosis Community Lab Costs • A man between age 50 and 70 who has at least one osteoporosis (greatly reduced rates) risk factor • Older than age 50 with a history of a broken bone • Taking medications, such as prednisone, aromatase inhibitors or Wellness Panel........................................................................ $20 Fasting anti-seizure drugs, that are associated with osteoporosis Includes screening for glucose, electrolytes, kidney, liver and • A postmenopausal woman who has recently stopped taking thyroid, plus complete blood count and lipid profile hormone therapy • A woman who experienced early menopause Diabetic Screening (A1c)...................................................... $5 The results of this test will indicate if you have or at risk for osteoporosis. Sickle Cell................................................................................ $6 If so, your doctor can offer treatment. PSA (Prostate Screening)...................................................... $8 Breathing Test This measures airflow and lung
    [Show full text]
  • Elevated Lipoprotein (A) Patient-Centered Education from the National Lipid Association
    Elevated Lipoprotein (a) Patient-Centered Education From the National Lipid Association What is Elevated Lipoprotein (a) ? Apo-B Apo (a) Lipoprotein (a) is a form of Low Density Lipoprotein (LDL) in which another protein, called Apo(a), is attached to each LDL particle as it carries cholesterol around in the body. Having elevated blood levels of Lipoprotein (a) raises a person’s risk of heart attack and stroke beyond what is normally seen from elevated LDL cholesterol alone. This is believed to be due to the Apo(a) protein, which may reduce the body’s ability to break down clots. Elevated Lipoprotein (a) is usually inherited from one parent. About 1 in 4 people in the population are believed to have elevated blood levels of Lipoprotein (a). African Americans may have higher levels. Besides genetics, Lipoprotein (a) levels may result from increased intake of some types of fats, and some medical conditions. Treatment of elevated Lipoprotein (a) is based on a person’s risk of heart attack or stroke. A healthy diet and lifestyle are the first step to reducing heart attack and stroke risk from elevated Lipoprotein (a). Medications also may help. ‘ Statins’ do not lower Lipoprotein (a) levels. However, statins are the most used medication for lowering heart attack and stroke risk in general, and so they are the most used medicine to treat risk from elevated Lipoprotein (a). Niacin can lower Lipoprotein (a) levels by 25-40%, as can PCSK9 inhibitors, but both are used less often. A new medication for lowering Lipoprotein (a) is being tested.
    [Show full text]
  • Commonly Used Lipidcentric ICD-10 (ICD-9) Codes
    Commonly Used Lipidcentric ICD-10 (ICD-9) Codes *This is not an all inclusive list of ICD-10 codes R.LaForge 11/2015 E78.0 (272.0) Pure hypercholesterolemia E78.3 (272.3) Hyperchylomicronemia (Group A) (Group D) Familial hypercholesterolemia Grütz syndrome Fredrickson Type IIa Chylomicronemia (fasting) (with hyperlipoproteinemia hyperprebetalipoproteinemia) Hyperbetalipoproteinemia Fredrickson type I or V Hyperlipidemia, Group A hyperlipoproteinemia Low-density-lipoid-type [LDL] Lipemia hyperlipoproteinemia Mixed hyperglyceridemia E78.4 (272.4) Other hyperlipidemia E78.1 (272.1) Pure hyperglyceridemia Type 1 Diabetes Mellitus (DM) with (Group B) hyperlipidemia Elevated fasting triglycerides Type 1 DM w diabetic hyperlipidemia Endogenous hyperglyceridemia Familial hyperalphalipoproteinemia Fredrickson Type IV Hyperalphalipoproteinemia, familial hyperlipoproteinemia Hyperlipidemia due to type 1 DM Hyperlipidemia, Group B Hyperprebetalipoproteinemia Hypertriglyceridemia, essential E78.5 (272.5) Hyperlipidemia, unspecified Very-low-density-lipoid-type [VLDL] Complex dyslipidemia hyperlipoproteinemia Elevated fasting lipid profile Elevated lipid profile fasting Hyperlipidemia E78.2 (272.2) Mixed hyperlipidemia (Group C) Hyperlipidemia (high blood fats) Broad- or floating-betalipoproteinemia Hyperlipidemia due to steroid Combined hyperlipidemia NOS Hyperlipidemia due to type 2 diabetes Elevated cholesterol with elevated mellitus triglycerides NEC Fredrickson Type IIb or III hyperlipoproteinemia with E78.6 (272.6)
    [Show full text]
  • Lipid Profile Abnormalities Seen in T2DM Patients in Primary Healthcare in Turkey: a Cross-Sectional Study Aclan Ozder
    Ozder Lipids in Health and Disease 2014, 13:183 http://www.lipidworld.com/content/13/1/183 RESEARCH Open Access Lipid profile abnormalities seen in T2DM patients in primary healthcare in Turkey: a cross-sectional study Aclan Ozder Abstract Background: Diabetes is characterized by chronic hyperglycemia and disturbances of carbohydrate, lipid and protein metabolism. We aimed to research association between serum lipid profile and blood glucose, hypothesizing that early detection and treatment of lipid abnormalities can minimize the risk for atherogenic cardiovascular disorder and cerebrovascular accident in patients with type 2 diabetes mellitus. Methods: Fasting blood glucose (FBG), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglyceride (TG) and glycated haemoglobin (HbA1c) levels were evaluated. A hepatic ultrasound was performed for every diabetic to evaluate hepatosteatosis. The study was done from January 2014 to June 2014 among 132 patients with T2DM who were admitted to outpatient clinic of Family Medicine department in a university hospital. The patients whose taking multi-vitamin supplementation or having hepatic, renal or metabolic bone disorders (including parathyroid related problems) were excluded from the study for the reason that those conditions might affect the carbohydrate and lipid metabolism in diabetes. Test of significance was calculated by unpaired student’s t test between cases and controls. Correlation studies (Pearson’s correlation) were performed between the variables of blood glucose and serum lipid profile. Significance was set at p<0.05. Results: Results of serum lipid profile showed that the mean values for TC, TG, HDL and LDL in female patients were 227.6 ± 57.7 mg/dl, 221.6 ± 101.1 mg/dl, 31.5 ± 6.7 mg/dl and 136.5 ± 43.7 mg/dl, respectively.
    [Show full text]
  • Lipid Guidelines 2018: Updates from ACC/AHA Guidelines 2013
    Lipid Guidelines 2018: Updates from ACC/AHA Guidelines 2013 Allen Adolphe M.D., Ph.D. FACP Professor and Vice Chief General Internal Medicine, University of New Mexico Objectives and Disclosures • Disclosures: NIH GRADE Study; Pharmaceutical Trials, none active now • Objectives – Know the four categories of high CVD risk from the ACC/AHA 2013 Lipid Guidelines (ATP IV) – Know what the major philosophical change between ATP III and ATP IV – Know what the ACC Expert Consensus Decision Pathway is and what changes in the ACC/AHA guidelines are suggested ATP IV: a little more abstract ATP III ATP IV • RISK FACTOR COUNTING • THERE IS NO TARGET • TREAT TO LDL GOAL • THE OF • ADDRESS NON-HDL TARGET INTENSITY STATIN THERAPY IS THE FOCUS OF TREATMENT ATP-IV (ACC-AHA 2013 Guidelines) • How many of you have adopted the ATP IV guidelines in your lipid practice by reducing the LDL-C by >50% for those at high risk of CVD? • How many of you believe that if the LDL-C too low it will place patients at risk for adverse effects? • How many of you treat patient with Familial Hyperlipidemia? A Comparative Analysis of Current Lipid Treatment Guidelines RISK ESTIMATORS • Risk estimators are derived from large studies in the United States or Europe. All include age, sex, total cholesterol, HDL-C, and systolic blood pressure as predictors. • However, ethnicity, treatment for hypertension, diabetes, and smoking status are only included in some; thus, patient risk may vary with different estimators. Outcomes are different between risk estimators • Outcome for the FRS is the most inclusive, predicting 10-year risk of coronary heart disease, cerebrovascular events, peripheral artery disease, or heart failure.
    [Show full text]
  • Increased Prebeta-High Density Lipoprotein, Apolipoprotein AI, And
    Increased prebeta-high density lipoprotein, apolipoprotein AI, and phospholipid in mice expressing the human phospholipid transfer protein and human apolipoprotein AI transgenes. X Jiang, … , J L Breslow, A R Tall J Clin Invest. 1996;98(10):2373-2380. https://doi.org/10.1172/JCI119050. Research Article Human plasma phospholipid transfer protein (PLTP) circulates bound to high density lipoprotein (HDL) and mediates both net transfer and exchange of phospholipids between different lipoproteins. However, its overall function in lipoprotein metabolism is unknown. To assess the effects of increased plasma levels of PLTP, human PLTP transgenic mice were established using the human PLTP gene driven by its natural promoter. One line of PLTP transgenic mice with moderate expression of PLTP mRNA and protein was obtained. The order of human PLTP mRNA expression in tissues was: liver, kidney, brain, small intestine > lung > spleen > heart, adipose tissue. Western blotting using a human PLTP monoclonal antibody revealed authentic human PLTP (Mr 80 kD) in plasma. Plasma PLTP activity was increased by 29% in PLTP transgenic mice. However, plasma lipoprotein analysis, comparing PLTP transgenic mice to control littermates, revealed no significant changes in the plasma lipoprotein lipids or apolipoproteins. Since previous studies have shown that human cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase only function optimally in human apoAI transgenic mice, the human PLTP transgenic mice were cross-bred with human apoAI transgenic mice. In the human apoAI transgenic background, PLTP expression resulted in increased PLTP activity (47%), HDL phospholipid (26%), cholesteryl ester (24%), free cholesterol (37%), and apoAI (22%). There was a major increase of apoAI in prebeta-HDL (56%) and […] Find the latest version: https://jci.me/119050/pdf Increased Pre␤-high Density Lipoprotein, Apolipoprotein AI, and Phospholipid in Mice Expressing the Human Phospholipid Transfer Protein and Human Apolipoprotein AI Transgenes Xian-cheng Jiang,* Omar L.
    [Show full text]