HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation

PloS One
Claudine TardyRudi Baron

Abstract

CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression in vitro and in vivo in the presence of CER-001 and native HDL (HDL3). CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL3 compared to non-lipidated apoA-I. In vivo, in an apoE-/- mouse "flow cessation model," in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progress...Continue Reading

References

Apr 27, 1999·Biochimica Et Biophysica Acta·S W SakrG H Rothblat
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·A T RemaleyH B Brewer
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·J KluckenG Schmitz
Mar 5, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Charles JoyceSilvia Santamarina-Fojo
May 24, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Roshni R SingarajaMichael R Hayden
Nov 6, 2003·JAMA : the Journal of the American Medical Association·Steven E NissenRichard Kerensky
Aug 17, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Susan M LessnerZorina S Galis
Nov 3, 2004·The Journal of Clinical Investigation·Ruth Frikke-SchmidtAnne Tybjaerg-Hansen
May 18, 2005·Journal of Lipid Research·Sanni SöderlundMarja-Riitta Taskinen
Oct 31, 2006·World Journal of Gastroenterology : WJG·Janine-K KruitFolkert Kuipers
Mar 20, 2008·Journal of Lipid Research·Ming-Shang KuoMark Rekhter
Jul 23, 2008·Perspectives in Vascular Surgery and Endovascular Therapy·Kimon Bekelis, Nicos Labropoulos
Sep 11, 2010·Expert Review of Cardiovascular Therapy·Justin M S Lee, Robin P Choudhury
Dec 3, 2010·Journal of Clinical Lipidology·W Virgil BrownErnst J Schaefer
Jan 24, 2013·Current Opinion in Lipidology·Elizabeth J Tarling
Apr 6, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Cédric Le MayPhilippe Costet
Jun 15, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Uwe J F Tietge, Albert K Groen
May 2, 2014·European Heart Journal·Jean-Claude TardifUNKNOWN Can HDL Infusions Significantly QUicken Atherosclerosis REgression (CHI-SQUARE) Investigators
May 3, 2014·Current Opinion in Lipidology·Ernst J SchaeferBela F Asztalos

❮ Previous
Next ❯

Citations

Nov 8, 2015·Pharmacology & Therapeutics·Maryam DarabiAnatol Kontush
Oct 27, 2015·Frontiers in Pharmacology·Ronald Barbaras
Nov 11, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Bradley K WackerDavid A Dichek
Oct 5, 2018·Journal of Personalized Medicine·Eftaxia-Konstantina ValantiDespina Sanoudou
Feb 19, 2017·Clinical Drug Investigation·Constance H KeyserlingJean-Louis Dasseux
Aug 9, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Dimitry A ChistiakovAlexander N Orekhov
Nov 7, 2018·Current Atherosclerosis Reports·Maki TsujitaAlan T Remaley
Sep 27, 2020·Biomedicines·Shifa Jebari-BenslaimanCésar Martín
Nov 3, 2016·Current Opinion in Lipidology·Kang H Zheng, Erik S G Stroes
Jan 5, 2021·Frontiers in Pharmacology·Emily E MorinAnna Schwendeman
Dec 15, 2020·Metabolism: Clinical and Experimental·Alice OssoliLaura Calabresi

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

GPEx
imageJ
Prism

Related Concepts

Related Feeds

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.