Evidence map›Paper›PMID 29321129›Full record

ArticleCirculation research2018

Novel Reversible Model of Atherosclerosis and Regression Using Oligonucleotide Regulation of the LDL Receptor.

Debapriya Basu, Yunying Hu, Lesley-Ann Huggins, Adam E Mullick, Mark J Graham, Tomasz Wietecha, Shelley Barnhart, Allison Mogul, Katharina Pfeiffer, Andreas Zirlik and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. β-carotene accelerates the resolution of atherosclerosis in mice.bioRxiv : the preprint server for biology · 2024
    Article
  10. Review
  11. Article
  12. Article
  13. Use of Animal Models for Investigating Cardioprotective Roles of SGLT2 Inhibitors.Journal of cardiovascular translational research · 2023
    Review
  14. Article
  15. Diagnostics of atherosclerosis: Overview of the existing methods.Frontiers in cardiovascular medicine · 2023
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Pig and Mouse Models of Hyperlipidemia and Atherosclerosis.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Debapriya BasuFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Yunying HuFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Lesley-Ann HugginsFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Adam E MullickFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Mark J GrahamFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Tomasz WietechaFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Shelley BarnhartFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Allison MogulFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Katharina PfeifferFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Andreas ZirlikFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Edward A FisherFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Karin E BornfeldtFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Florian WilleckeFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.).
Ira J GoldbergFrom the Department of Medicine, New York University Langone Health, New York (D.B., Y.H., L.-A.H., A.M., E.A.F., I.J.G.); Ionis Pharmaceuticals, Carlsbad, CA (A.E.M., M.J.G.); Division of Cardiology, Department of Medicine (T.W.), Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, UW Diabetes Institute (S.B., K.E.B.), and Department of Pathology (K.E.B.), University of Washington, Seattle; and Department of Cardiology and Angiology I, Heart Center, Freiburg University, Germany (K.P., A.Z., F.W.). ira.goldberg@nyumc.org.
NYU Langone Health · USIonis Pharmaceuticals (United States) · USUniversity of Washington · US

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Karin E Bornfeldt · 1986 to 2026
$41.4M
Role of Serum Amyloid A in Diabetic Vascular DiseaseP01HL092969 · NHLBI · UNIVERSITY OF WASHINGTON · PI VAISAR, TOMAS · 2008 to 2019
$23.5M
Pathways of Tissue Lipid UptakeR01HL045095 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ABUMRAD, NADA A., GOLDBERG, IRA J · 1991 to 2024
$6.9M
Diabetes-Mediated Effects on Myeloid Precursors and Vascular ComplicationsR01DK095684 · NIDDK · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI FISHER, EDWARD A, GOLDBERG, IRA J · 2012 to 2016
$2.7M
Obesity and Arterial MetabolismR01HL126028 · NHLBI · UNIVERSITY OF WASHINGTON · PI BORNFELDT, KARIN E. · 2015 to 2018
$1.7M
APOC3, HDL Function and Cardiovascular Complications of T1DMDP3DK108209 · NIDDK · UNIVERSITY OF WASHINGTON · PI BORNFELDT, KARIN E., HEINECKE, JAY W · 2015 to 2015
$1.6M
NHLBI NIH HHS P01 HL092969NHLBI NIH HHS R01 HL045095NHLBI NIH HHS R01 HL126028NIDDK NIH HHS DP3 DK108209NIDDK NIH HHS P30 DK017047NIDDK NIH HHS R01 DK095684
6 · The paper itself

Abstract

rationaleAnimal models have been used to explore factors that regulate atherosclerosis. More recently, they have been used to study the factors that promote loss of macrophages and reduction in lesion size after lowering of plasma cholesterol levels. However, current animal models of atherosclerosis regression require challenging surgeries, time-consuming breeding strategies, and methods that block liver lipoprotein secretion.

objectiveWe sought to develop a more direct or time-effective method to create and then reverse hypercholesterolemia and atherosclerosis via transient knockdown of the hepatic LDLR (low-density lipoprotein receptor) followed by its rapid restoration. METHODS AND

resultsWe used antisense oligonucleotides directed to LDLR mRNA to create hypercholesterolemia in wild-type C57BL/6 mice fed an atherogenic diet. This led to the development of lesions in the aortic root, aortic arch, and brachiocephalic artery. Use of a sense oligonucleotide replicating the targeted sequence region of the LDLR mRNA rapidly reduced circulating cholesterol levels because of recovery of hepatic LDLR expression. This led to a decrease in macrophages within the aortic root plaques and brachiocephalic artery, that is, regression of inflammatory cell content, after a period of 2 to 3 weeks.

conclusionsWe have developed an inducible and reversible hepatic LDLR knockdown mouse model of atherosclerosis regression. Although cholesterol reduction decreased early en face lesions in the aortic arches, macrophage area was reduced in both early and late lesions within the aortic sinus after reversal of hypercholesterolemia. Our model circumvents many of the challenges associated with current mouse models of regression. The use of this technology will potentially expedite studies of atherosclerosis and regression without use of mice with genetic defects in lipid metabolism.

Indexed as

Disease Models, AnimalAnimalsAortaAtherosclerosisCholesterolFemaleGene Knockdown TechniquesMaleMiceMice, Inbred C57BLOligonucleotides, AntisenseReceptors, LDLCholesterolOligonucleotides, AntisenseReceptors, LDLcholesterol, LDLlipidslipoproteinmacrophagemetabolism

Identifiers

PMID29321129
PMCPMC5815899
OpenAlexW2783888432

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.