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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2014

Open Access 01-12-2014 | Original investigation

Immunization with advanced glycation end products modified low density lipoprotein inhibits atherosclerosis progression in diabetic apoE and LDLR null mice

Authors: Lin Zhu, Zhiqing He, Feng Wu, Ru Ding, Qixia Jiang, Jiayou Zhang, Min Fan, Xing Wang, Bengtsson Eva, Nilsson Jan, Chun Liang, Zonggui Wu

Published in: Cardiovascular Diabetology | Issue 1/2014

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Abstract

Background

Diabetes accelerates atherosclerosis through undefined molecular mechanisms. Hyperglycemia induces formation of advanced glycation end product (AGE)-modified low-density lipoprotein (LDL). Anti-AGE-LDL autoantibodies favor atherosclerosis (AS) progression in humans, while anti oxidized LDL immunization inhibits AS in hypercholesterolemic, non-diabetic mice. We here investigated if AGE-LDL immunization protects against AS in diabetic mice.

Methods

After diabetes induction with streptozotocin and high fat diet, both low density lipoprotein receptor (LDLR)-/- and apoE female mice were randomized to: AGE-LDL immunization with aluminum hydroxide (Alum) adjuvant; Alum alone; or PBS.

Results

AGE-LDL immunization: significantly reduced AS; induced specific plasma IgM and IgG antibodies; upregulated splenic Th2, Treg and IL-10 levels, without altering Th1 or Th17 cells; and increased serum high density lipoprotein(HDL) while numerically lowering HbA1c levels.

Conclusions

Subcutaneous immunization with AGE-LDL significantly inhibits atherosclerosis progression in hyperlipidemic diabetic mice possibly through activation of specific humoral and cell mediated immune responses and metabolic control improvement.
Appendix
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Metadata
Title
Immunization with advanced glycation end products modified low density lipoprotein inhibits atherosclerosis progression in diabetic apoE and LDLR null mice
Authors
Lin Zhu
Zhiqing He
Feng Wu
Ru Ding
Qixia Jiang
Jiayou Zhang
Min Fan
Xing Wang
Bengtsson Eva
Nilsson Jan
Chun Liang
Zonggui Wu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2014
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-014-0151-6

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