Recombinant antibodies to an oxidized low-density lipoprotein epitope induce rapid regression of atherosclerosis in apobec-1(-/-)/low-density lipoprotein receptor(-/-) mice.

Schiopu, Alexandru; Frendéus, Björn; Jansson, Bo; Söderberg, Ingrid; Ljungcrantz, Irena; Araya, Zufan; Shah, Prediman K; Carlsson, Roland; Nilsson, Jan; Nordin Fredrikson, Gunilla

Recombinant antibodies to an oxidized low-density lipoprotein epitope induce rapid regression of atherosclerosis in apobec-1(-/-)/low-density lipoprotein receptor(-/-) mice.

Mark

Schiopu, Alexandru ^LU ; Frendéus, Björn ; Jansson, Bo ; Söderberg, Ingrid ^LU ; Ljungcrantz, Irena ^LU ; Araya, Zufan ; Shah, Prediman K ; Carlsson, Roland ; Nilsson, Jan ^LU and Nordin Fredrikson, Gunilla ^LU (2007) In Journal of the American College of Cardiology 50(24). p.2313-2318

Abstract: OBJECTIVES: The present study tested the hypothesis that treatment with human recombinant immunoglobulin G1 (IgG1) antibodies against a specific oxidized low-density lipoprotein (oxLDL) epitope will induce regression of existing atherosclerotic lesions in LDL receptor-deficient mice expressing apolipoprotein B-100 (apoB-100) (Apobec-1(-/-)/LDLR(-/-)). BACKGROUND: Oxidized LDL plays an essential role in the pathogenesis of atherosclerosis. We previously showed that an antibody against oxLDL reduces progression of atherosclerosis in mice. METHODS: Apobec-1(-/-)/LDLR(-/-) mice were fed a high-fat diet until they were 24 weeks and were subsequently transferred to chow. Starting at 25 weeks, mice were given 3 weekly injections of either of 2... (More); OBJECTIVES: The present study tested the hypothesis that treatment with human recombinant immunoglobulin G1 (IgG1) antibodies against a specific oxidized low-density lipoprotein (oxLDL) epitope will induce regression of existing atherosclerotic lesions in LDL receptor-deficient mice expressing apolipoprotein B-100 (apoB-100) (Apobec-1(-/-)/LDLR(-/-)). BACKGROUND: Oxidized LDL plays an essential role in the pathogenesis of atherosclerosis. We previously showed that an antibody against oxLDL reduces progression of atherosclerosis in mice. METHODS: Apobec-1(-/-)/LDLR(-/-) mice were fed a high-fat diet until they were 24 weeks and were subsequently transferred to chow. Starting at 25 weeks, mice were given 3 weekly injections of either of 2 recombinant human IgG1 antibodies (IEI-E3 or 2D03) against a malondialdehyde-modified apoB-100 peptide sequence. RESULTS: At 25 weeks, atherosclerotic lesions covered 10.3 +/- 3.7% of the descending aorta. Transfer to chow diet resulted in a modest regression of atherosclerosis over a 5-week period (8.28 +/- 4.36%; p = NS). Antibody treatment induced additional regression of atherosclerosis by 50% (2D03; p = 0.001) and 36% (IEI-E3; p = 0.004) compared with control IgG1. The 2D03 treatment also reduced plaque inflammation, enhanced plaque expression of the adenosine triphosphate-binding cassette transporter A1, and inhibited expression of monocyte chemoattractant protein-1 in cultured monocytes. CONCLUSIONS: Human IgG1 against a specific oxLDL epitope can induce rapid and substantial regression of atherosclerotic lesions, possibly by stimulating lipid efflux and inhibiting macrophage recruitment. These recombinant human antibodies could represent a novel strategy for rapid regression/stabilization of atherosclerotic lesions. (Less)

Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/1035434

author

Schiopu, Alexandru ^LU ; Frendéus, Björn ; Jansson, Bo ; Söderberg, Ingrid ^LU ; Ljungcrantz, Irena ^LU ; Araya, Zufan ; Shah, Prediman K ; Carlsson, Roland ; Nilsson, Jan ^LU and Nordin Fredrikson, Gunilla ^LU

organization

Cardiovascular Research - Immunity and Atherosclerosis (research group)

publishing date

2007

type

Contribution to journal

publication status

published

subject

Cardiac and Cardiovascular Systems

keywords

Recombinant Proteins: therapeutic use, Oxidized LDL: physiology, Receptors, Peptide Fragments: immunology, Immunologic Factors: therapeutic use, Immunoglobulin G: therapeutic use, Cytidine Deaminase: physiology, Atherosclerosis: pathology, Atherosclerosis: metabolism, Atherosclerosis: drug therapy, ATP-Binding Cassette Transporters: metabolism, Apolipoprotein B-100: immunology

in

Journal of the American College of Cardiology

volume

50

issue

24

pages

2313 - 2318

publisher

Elsevier

external identifiers

pmid:18068040
wos:000251803800006
scopus:36649010572

ISSN

0735-1097

DOI

10.1016/j.jacc.2007.07.081

language

English

LU publication?

yes

id

84e544e2-15dd-4b14-a4a1-1b42303841af (old id 1035434)

alternative location

http://www.ncbi.nlm.nih.gov/pubmed/18068040?dopt=Abstract

date added to LUP

2016-04-01 11:46:29

date last changed

2022-04-20 21:36:09

@article{84e544e2-15dd-4b14-a4a1-1b42303841af,
  abstract     = {{OBJECTIVES: The present study tested the hypothesis that treatment with human recombinant immunoglobulin G1 (IgG1) antibodies against a specific oxidized low-density lipoprotein (oxLDL) epitope will induce regression of existing atherosclerotic lesions in LDL receptor-deficient mice expressing apolipoprotein B-100 (apoB-100) (Apobec-1(-/-)/LDLR(-/-)). BACKGROUND: Oxidized LDL plays an essential role in the pathogenesis of atherosclerosis. We previously showed that an antibody against oxLDL reduces progression of atherosclerosis in mice. METHODS: Apobec-1(-/-)/LDLR(-/-) mice were fed a high-fat diet until they were 24 weeks and were subsequently transferred to chow. Starting at 25 weeks, mice were given 3 weekly injections of either of 2 recombinant human IgG1 antibodies (IEI-E3 or 2D03) against a malondialdehyde-modified apoB-100 peptide sequence. RESULTS: At 25 weeks, atherosclerotic lesions covered 10.3 +/- 3.7% of the descending aorta. Transfer to chow diet resulted in a modest regression of atherosclerosis over a 5-week period (8.28 +/- 4.36%; p = NS). Antibody treatment induced additional regression of atherosclerosis by 50% (2D03; p = 0.001) and 36% (IEI-E3; p = 0.004) compared with control IgG1. The 2D03 treatment also reduced plaque inflammation, enhanced plaque expression of the adenosine triphosphate-binding cassette transporter A1, and inhibited expression of monocyte chemoattractant protein-1 in cultured monocytes. CONCLUSIONS: Human IgG1 against a specific oxLDL epitope can induce rapid and substantial regression of atherosclerotic lesions, possibly by stimulating lipid efflux and inhibiting macrophage recruitment. These recombinant human antibodies could represent a novel strategy for rapid regression/stabilization of atherosclerotic lesions.}},
  author       = {{Schiopu, Alexandru and Frendéus, Björn and Jansson, Bo and Söderberg, Ingrid and Ljungcrantz, Irena and Araya, Zufan and Shah, Prediman K and Carlsson, Roland and Nilsson, Jan and Nordin Fredrikson, Gunilla}},
  issn         = {{0735-1097}},
  keywords     = {{Recombinant Proteins: therapeutic use; Oxidized LDL: physiology; Receptors; Peptide Fragments: immunology; Immunologic Factors: therapeutic use; Immunoglobulin G: therapeutic use; Cytidine Deaminase: physiology; Atherosclerosis: pathology; Atherosclerosis: metabolism; Atherosclerosis: drug therapy; ATP-Binding Cassette Transporters: metabolism; Apolipoprotein B-100: immunology}},
  language     = {{eng}},
  number       = {{24}},
  pages        = {{2313--2318}},
  publisher    = {{Elsevier}},
  series       = {{Journal of the American College of Cardiology}},
  title        = {{Recombinant antibodies to an oxidized low-density lipoprotein epitope induce rapid regression of atherosclerosis in apobec-1(-/-)/low-density lipoprotein receptor(-/-) mice.}},
  url          = {{http://dx.doi.org/10.1016/j.jacc.2007.07.081}},
  doi          = {{10.1016/j.jacc.2007.07.081}},
  volume       = {{50}},
  year         = {{2007}},
}

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Recombinant antibodies to an oxidized low-density lipoprotein epitope induce rapid regression of atherosclerosis in apobec-1(-/-)/low-density lipoprotein receptor(-/-) mice.