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

  • Lin Zhu
  • Zhiqing He
  • Feng Wu
  • Ru Ding
  • Qixia Jiang
  • Jiayou Zhang
  • Min Fan
  • Xing Wang
  • Eva Bengtsson
  • Jan Nilsson
  • Chun Liang
  • Zonggui Wu
Publishing year: 2014
Language: English
Publication/Series: Cardiovascular Diabetology
Volume: 13
Document type: Journal article
Publisher: BioMed Central

Abstract english

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.


  • Cardiac and Cardiovascular Systems
  • Immunization
  • Advanced glycation end products
  • Low density lipoprotein
  • Atherosclerosis
  • Diabetes


  • Cardiovascular Research - Immunity and Athersosclerosis
  • ISSN: 1475-2840
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00