title: Osteopontin: a potential biomarker for heart failure and reverse remodeling after left ventricular assist device support.
abstract: BACKGROUND
  Left ventricular assist device (LVAD) support in end-stage heart failure (HF) leads to recovery of the patient's condition, size reduction of cardiomyocytes, and also volume reduction and change in the composition of the extracellular matrix (ECM). Myocardial expression of ECM osteopontin (OPN) protein increases with the severity of HF. We analyzed whether OPN messenger RNA expression in heart tissue and/or OPN protein in plasma are associated with reverse remodeling during LVAD support.
  
  
  METHODS
  Plasma and heart tissue specimens of 22 end-stage HF patients before and after LVAD implantation and subsequent heart transplantation (HTx) were used to determine the concentrations of OPN protein (EIA) and OPN messenger RNA (mRNA) by quantitative polymerase chain reaction. Immunohistochemistry (IHC) and in situ hybridization (ISH) were performed to locate OPN protein and mRNA.
  
  
  RESULTS
  The high OPN protein levels in plasma of HF patients did not differ significantly before and after LVAD support in ischemic heart disease (IHD) (pre-LVAD 167 ± 32 ng/ml; post-LVAD 165 ± 28 ng/ml) and in dilated cardiomyopathy (DCM) (pre-LVAD 99 ± 12 ng/ml; post-LVAD (142 ± 6 ng/ml). The OPN plasma levels after HTx decreased to control levels (IHD, 48 ± 6; DCM, 40 ± 5; control, 31 ± 3 ng/ml). In contrast, expression of OPN mRNA in heart biopsy specimens decreased significantly after LVAD support (the relative quantity decreased > 90% in IHD and 50% in DCM). ISH and IHC revealed that OPN was present in cardiomyocytes and in the ECM.
  
  
  CONCLUSIONS
  Levels of OPN mRNA in the myocardium of HF patients showed a significant decrease after LVAD support but OPN protein expression did not. LVAD support only induced a decrease of OPN plasma levels in individual patients, whereas OPN plasma levels reduced significantly in all patients after HTx.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marguérite E I
authors.initials: ME
authors.lastname: Schipper
authors.forename: Maaike R
authors.initials: MR
authors.lastname: Scheenstra
authors.forename: Joyce
authors.initials: J
authors.lastname: van Kuik
authors.forename: Dick F
authors.initials: DF
authors.lastname: van Wichen
authors.forename: Petra
authors.initials: P
authors.lastname: van der Weide
authors.forename: Hub F J
authors.initials: HF
authors.lastname: Dullens
authors.forename: Jaap
authors.initials: J
authors.lastname: Lahpor
authors.forename: Nicolaas
authors.initials: N
authors.lastname: de Jonge
authors.forename: Roel A
authors.initials: RA
authors.lastname: De Weger
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006333:Heart Failure / Q000097:blood / Q000378:metabolism* / Q000628:therapy*; D016027:Heart Transplantation; D006353:Heart-Assist Devices / Q000009:adverse effects; D006801:Humans; D017403:In Situ Hybridization; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D053495:Osteopontin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism*; D016896:Treatment Outcome; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D053495:Osteopontin