title: Advanced glycation end products induced immune maturation of dendritic cells controls heart failure through NF-κB signaling pathway.
abstract: OBJECTIVE
  It is commonly believed that diabetes is an important contributor to heart failure (HF) development. However, the detail effect of diabetogenesis on HF is controversy: both beneficial and harmful roles were reported. In the present study, we aim to explore the unambiguous action of diabetes on chronic HF progression and the underlying mechanism.
  
  
  METHODS
  Diabetes and myocardial infarction (MI) were induced by streptozotocin (STZ) injection and left-sided thoracotomy and left anterior descending coronary artery (LAD) ligation, respectively. Pyridoxamine was used as the antagonist of advanced glycation end products (AGEs). Adult male SD rats were assigned to 5 groups: Sham; MI; Diabetes (D); Diabetes+MI (DMI) and DMI+pyridoxamine (DMI+P). Animals were sacrificed at the end of 12weeks. The comparison of LV myocardium was made between border zone from MI or DMI animals and control LV tissues from sham-operated animals. Cardiomyocytes and dendritic cells were prepared from the Sprague-Dawley rats and cocultured in the presence or absence of AGEs.
  
  
  RESULTS
  DMI group showed highest level of AGEs and inflammatory markers, which were significantly reduced in the presence of pyridoxamine. In vitro experiment disclosed AGEs could stimulate DCs differentiation and promote cytokines production, finally upregulated hypertrophy-related genes expression in cardiocytes. Intervention DCs differentiation was sufficient to improve cardiocytes morphology.
  
  
  CONCLUSIONS
  Our results clearly demonstrate that diabetes would promote chronic HF progression at least in part through stimulating DCs differentiation and series downstream inflammatory responses induced by AGEs.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: weiweiivy82@126.com.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Chen
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Shaorui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Engineering Laboratory of Guangdong Province for Druggability and New Drug Evaluation, China.
authors.forename: Heqing
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Engineering Laboratory of Guangdong Province for Druggability and New Drug Evaluation, China. Electronic address: liupq@mail.sysu.edu.cn.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D061251:Primary Cell Culture; D011733:Pyridoxamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction; D013311:Streptozocin
chemical_list: D002316:Cardiotonic Agents; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D013311:Streptozocin; D011733:Pyridoxamine
keywords: Advanced glycation end product; Dendritic cells; Heart failure; NF-κB signaling