title: Nicotine Induces Cardiomyocyte Hypertrophy Through TRPC3-Mediated Ca2+/NFAT Signalling Pathway.
abstract: Nicotine is thought to be an important risk factor for the development of cardiovascular diseases. However, the effects of nicotine on cardiomyocyte hypertrophy are poorly understood. The present study was designed to explore the role of nicotine in cardiomyocyte hypertrophy and its underlying mechanism.
  
  
  
  We used primary cardiomyocytes isolated from Wistar rats to examine the effects of nicotine on intracellular Ca2+mobilization and hypertrophy determined by immunofluorescence, quantitative polymerase chain reaction, and western blot analysis. A luciferase reporter assay was used to examine the activity of NFAT signalling.
  
  
  
  We found that nicotine caused cardiomyocyte hypertrophy, which was accompanied by increased intracellular Ca2+. Nicotine-enhanced intracellular Ca2+concentration ([Ca2+]i) was significantly abolished by store-operated Ca2+entry (SOCE) and TRPC inhibitors. Knockdown of TRPC3 significantly decreased nicotine-induced SOCE and hypertrophy. Moreover, calcineurin-nuclear factor of activated T cells (NFAT) is involved in TRPC3-mediated Ca2+signalling and cardiomyocyte hypertrophy. Notably, upregulation of TRPC3 by nicotine requires TRPC3-mediated Ca2+influx and calcineurin-NFAT signalling activation.
  
  
  
  Our findings demonstrate that the prohypertrophic effect of nicotine on cardiomyocytes is dependent on enhanced TRPC3 expression through a calcium-dependent regulatory loop, which could become a potential target for prevention and treatment of cardiac hypertrophy.
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Si
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Ju
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: You
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Yan-Song
authors.initials: YS
authors.lastname: Ning
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Feng-Quan
authors.initials: FQ
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Dong
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Wen-Qian
authors.initials: WQ
authors.lastname: Yu
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China. Electronic address: wangtongjian0425@126.com.
authors.forename: Tong-Jian
authors.initials: TJ
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China. Electronic address: cijnmd@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Qiao
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D049108:Cell Enlargement / Q000187:drug effects*; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology*; D050778:NFATC Transcription Factors / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D017208:Rats, Wistar; D050052:TRPC Cation Channels / Q000502:physiology*
chemical_list: D005731:Ganglionic Stimulants; D050778:NFATC Transcription Factors; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D009538:Nicotine