title: Vascular effects of cardiotrophin-1: a role in hypertension?
abstract: OBJECTIVE
  To investigate cardiotrophin-1 (CT-1) effects and regulation in vascular smooth muscle cells (VSMCs) in vitro and in aortic tunica media ex vivo in normotensive Wistar rats and spontaneously hypertensive rats (SHRs).
  
  
  RESULTS
  CT-1 expression was quantified by real-time reverse-transcription PCR and western blotting. CT-1-activated intracellular pathways were assessed by western bloting analysis. Proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ki67 immunodetection, and cell hypertrophy by planimetry. Extracellular matrix components were quantified by real-time reverse-transcription PCR and western blot, and metalloproteinases activities by zymography. VSMCs from Wistar rats and SHRs expressed spontaneously CT-1 at the mRNA and the protein level, with a two-fold more increase in SHRs. CT-1 phosphorylated p42/44 mitogen-activated protein kinase, p38 mitogen-activated protein kinase, Akt and Stat-3 in both strains. CT-1 stimulated VSMCs proliferation and hypertrophy in both strains, with an enhanced stimulation in SHRs. CT-1 increased the secretion of collagen type I and fibronectin in VSMCs and aortic tunica media of Wistar rats and SHRs, with greater magnitude in SHRs. In SHRs VSMCs in vitro and ex vivo, CT-1 increased the secretion of collagen type III and elastin and the expression of tissue inhibitors of metalloproteinases, without altering metalloproteinase activity. These effects were blocked by CT-1 receptor antibodies. Aldosterone treatment increased CT-1 expression in VSMCs and aortic tunica media from both strains, with a greater magnitude in SHRs.
  
  
  CONCLUSIONS
  CT-1 induces VSMCs proliferation, hypertrophy and extracellular matrix production, and is upregulated in hypertension and by aldosterone. CT-1 may represent a new target of vascular wall remodeling in hypertension.
authors.affiliation: Inserm U961, Faculty of Medicine, Vandoeuvre-les-Nancy, France.
authors.forename: Natalia
authors.initials: N
authors.lastname: Lopez-Andres
authors.forename: Maria A
authors.initials: MA
authors.lastname: Fortuno
authors.forename: Javier
authors.initials: J
authors.lastname: Diez
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: Patrick
authors.initials: P
authors.lastname: Lacolley
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; C092073:cardiotrophin 1