title: Interleukin 18 promotes myofibroblast activation of valvular interstitial cells.
abstract: BACKGROUND
  Calcific aortic valve disease is the main heart valve disease in the elderly. Valvular interstitial cells (VICs) play an important role in the process of valve calcification. Interleukin 18 (IL-18) is expressed in stenosis aortic valves and is positively related with the clinical severity of aortic stenosis. However, the role of IL-18 in aortic valve calcification remains unclear. This study examined whether IL-18 promotes myofibroblast and/or osteoblast transdifferention of VICs. Porcine VICs were isolated and treated with recombinant porcine IL-18.
  
  
  METHODS
  Porcine VICs were cultured and treated with IL-18. Gene and protein expression of myofibroblastic and osteoblastic markers were tested and nuclear factor κB (NF-κB) phosphorylation was also analyzed. Alkaline phosphatase (ALP) staining and activity assay were also performed.
  
  
  RESULTS
  Our experiments demonstrated that IL-18 significantly enhanced alpha-smooth muscle actin (α-SMA) gene and protein expression. IL-18 treatment also promoted the expression of osteopontin (OPN) and runt-related transcription factor 2 (Runx2) mRNA, although OPN and Runx2 protein expressions were not changed. IL-18 could induce ALP activity in the presence of conditioning medium. We also demonstrated that IL-18 markedly enhanced NF-κB p65 phosphorylation in VICs.
  
  
  CONCLUSIONS
  Together these results suggest that IL-18 promotes the myofibroblast differentiation of VICs and accelerates calcification in the presence of conditioning medium via the NF-κB pathway.
authors.affiliation: Department of Cardiovascular Surgery, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cardiovascular Surgery, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Jinfu
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Busheng
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: zhudanmd@163.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Cardiovascular Surgery, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China. Electronic address: wuyh@sohu.com.
authors.forename: Yanhu
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000378:metabolism / Q000473:pathology; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin / Q000378:metabolism; D010766:Phosphorylation; D013552:Swine; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000199:Actins; D050659:Core Binding Factor Alpha 1 Subunit; D020382:Interleukin-18; D051996:Transcription Factor RelA; D053495:Osteopontin
keywords: Interleukin 18; Myofibroblast; Valvular heart disease; Valvular interstitial cells; α-Smooth muscle actin