title: Advanced glycation end-products accelerate the cardiac aging process through the receptor for advanced glycation end-products/transforming growth factor-β-Smad signaling pathway in cardiac fibroblasts.
abstract: OBJECTIVE
  The current study was carried out to evaluate the effect of advanced glycation end-products (AGE) on cardiac aging and to explore its underlying mechanisms.
  
  
  METHODS
  Neonatal rat cardiac fibroblasts were cultured and divided into four groups: control; AGE; AGE + receptor for AGE antibody and AGE + SB431542 (transforming growth factor-β [TGF-β]/Smad signaling pathway inhibitor, 10 μmol/L) group. After being cultured for 48 h, the cells were harvested and the senescence-associated beta-galactosidase expression was analyzed. Then the level of p16, TGF-β, Smad/p-smad and matrix metalloproteinases-2 was evaluated by western blot.
  
  
  RESULTS
  Significantly increased senescence-associated beta-galactosidase activity as well as p16 level was observed in the AGE group. Furthermore, AGE also significantly increased the TGF-β1, p-smad2/3 and metalloproteinases-2 expression in cardiac fibroblasts (all P < 0.01). Meanwhile, either pretreatment with receptor for AGE-Ab or SB431542 significantly inhibited the upregulated cardiac senescence (beta-galactosidase activity and P16) and fibrosis-associated (TGF-β1, p-smad2/3 and metalloproteinases-2) markers induced by AGE.
  
  
  CONCLUSIONS
  Taken together, all these results suggested that AGE are an important factor for cardiac aging and fibrosis, whereas the receptor for AGE and TGF-β/Smad signaling pathway might be involved in the AGE-induced cardiac aging process.
authors.affiliation: Department of Gerontlogy, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Gerontlogy, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Junhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gerontlogy, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Shiling
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gerontlogy, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|Department of Cardioangiology, Shengze Hospital of Jiangsu Province, Suzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D051785:Smad Proteins / Q000096:biosynthesis / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D012313:RNA
keywords: advanced glycation end-products; cardiac aging; receptor for advanced glycation end-products; transforming growth factor-β-Smad pathway