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

Cardiovascular Diabetology

Original Investigation

Zhiqing He¹  Qixia Jiang¹  Ru Ding¹  Min Fan¹  Xing Wang¹  Jiayou Zhang¹  Chun Liang¹  Zonggui Wu¹  Lin Zhu²  Feng Wu³  Nilsson Jan⁴  Bengtsson Eva⁴ 

[1] Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, 200003, Shanghai, People’s Republic of China;Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, 200003, Shanghai, People’s Republic of China;457th hospital of PLA, Wuhan, People’s Republic of China;Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, 200003, Shanghai, People’s Republic of China;Department of Research, Center for Stem Cell Biology, Roger Williams Medical Center, Boston University School of Medicine, Providence, RI, USA;Experimental Cardiovascular Research, CRC 91:12, Lund University, SE-205 02, Malmö, Sweden;

关键词: Immunization;    Advanced glycation end products;    Low density lipoprotein;    Atherosclerosis;    Diabetes;   

DOI  :  10.1186/s12933-014-0151-6

 received in 2014-09-15, accepted in 2014-10-22,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundDiabetes 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.MethodsAfter 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.ResultsAGE-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.ConclusionsSubcutaneous 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.

【 授权许可】

Unknown   
© Zhu et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.