title: Circulating growth differentiation factor-15 correlates with myocardial fibrosis in patients with non-ischaemic dilated cardiomyopathy and decreases rapidly after left ventricular assist device support.
abstract: OBJECTIVE
  Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine and is emerging as a biomarker of cardiac remodelling. Left ventricular assist devices (LVADs) provide unloading of the left ventricle, resulting in partial reverse remodelling. Our aim was to study GDF-15 in patients with a non-ischaemic dilated cardiomyopathy (DCM) during LVAD support.
  
  
  RESULTS
  We analysed circulating GDF-15 in 30 patients before and 1, 3, and 6 months after LVAD implantation and before heart transplantation or explantation. In addition, mRNA and protein expression of GDF-15 were evaluated in myocardial tissue obtained prior to and after LVAD support. Circulating GDF-15 was significantly higher before LVAD implantation as compared with healthy controls (P < 0.001). After 1 month of mechanical support, GDF-15 levels were significantly decreased compared with pre-implantation levels (P < 0.001) and remained stable thereafter. Circulating GDF-15 was significantly correlated with kidney function and the severity of myocardial fibrosis. Interestingly, GDF-15 mRNA and protein expression in the myocardium were hardly detectable.
  
  
  CONCLUSIONS
  High circulating levels of GDF-15 in patients with end-stage non-ischaemic DCM correlate with myocardial fibrosis and kidney function and decline strongly after 1 month of mechanical unloading, remaining stable thereafter. However, cardiac mRNA and protein expression of GDF-15 are very low, suggesting that the heart is not an important source of GDF-15 production in these patients.
authors: Department of Cardiology, University Medical Centre Utrecht, The Netherlands. s.lok@umcutrecht.nl
authors: Sjoukje I
authors: SI
authors: Lok
authors: Bjorn
authors: B
authors: Winkens
authors: Roel
authors: R
authors: Goldschmeding
authors: Ankie J P
authors: AJ
authors: van Geffen
authors: Fay M A
authors: FM
authors: Nous
authors: Joyce
authors: J
authors: van Kuik
authors: Petra
authors: P
authors: van der Weide
authors: Corinne
authors: C
authors: Klöpping
authors: J Hans
authors: JH
authors: Kirkels
authors: Jaap R
authors: JR
authors: Lahpor
authors: Pieter A
authors: PA
authors: Doevendans
authors: Nicolaas
authors: N
authors: de Jonge
authors: Roel A
authors: RA
authors: de Weger
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D005260:Female; D005355:Fibrosis / Q000097:blood* / Q000473:pathology; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006305:Health Status Indicators; D006352:Heart Ventricles / Q000473:pathology*; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015397:Program Evaluation; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000628:therapy*; D020257:Ventricular Remodeling
chemical_list: D016207:Cytokines; D055436:Growth Differentiation Factor 15