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

Zhu, Lin; He, Zhiqing; Wu, Feng; Ding, Ru; Jiang, Qixia; Zhang, Jiayou; Fan, Min; Wang, Xing; Bengtsson, Eva LU and Nilsson, Jan LU , et al. (2014) In Cardiovascular Diabetology 13.
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... (More)
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. (Less)
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type
Contribution to journal
publication status
published
subject
keywords
Immunization, Advanced glycation end products, Low density lipoprotein, Atherosclerosis, Diabetes
in
Cardiovascular Diabetology
volume
13
publisher
BioMed Central
external identifiers
  • wos:000346064300001
  • scopus:84920847396
ISSN
1475-2840
DOI
10.1186/s12933-014-0151-6
language
English
LU publication?
yes
id
819656da-1cd1-4040-85ff-153ac8433a4f (old id 4965656)
date added to LUP
2015-02-03 07:03:19
date last changed
2017-09-24 03:52:21
@article{819656da-1cd1-4040-85ff-153ac8433a4f,
  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.},
  articleno    = {151},
  author       = {Zhu, Lin and He, Zhiqing and Wu, Feng and Ding, Ru and Jiang, Qixia and Zhang, Jiayou and Fan, Min and Wang, Xing and Bengtsson, Eva and Nilsson, Jan and Liang, Chun and Wu, Zonggui},
  issn         = {1475-2840},
  keyword      = {Immunization,Advanced glycation end products,Low density lipoprotein,Atherosclerosis,Diabetes},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {Cardiovascular Diabetology},
  title        = {Immunization with advanced glycation end products modified low density lipoprotein inhibits atherosclerosis progression in diabetic apoE and LDLR null mice},
  url          = {http://dx.doi.org/10.1186/s12933-014-0151-6},
  volume       = {13},
  year         = {2014},
}