title: Brain natriuretic peptide is produced both by cardiomyocytes and cells infiltrating the heart in patients with severe heart failure supported by a left ventricular assist device.
abstract: BACKGROUND
  Brain natriuretic peptide (BNP) is a cardiac neurohormone synthesized in cardiac ventricles as a result of increased wall stress. Left ventricular assist device (LVAD) support in patients with end-stage heart failure results in reduced wall stress and therefore may change BNP levels in the heart.
  
  
  METHODS
  BNP plasma levels were measured in 17 patients with end-stage HF before LVAD implantation and at 1 week, 1 month, and 3 months after LVAD support. BNP-messenger RNA (mRNA) expression in cardiac biopsy specimens of 27 patients before and after LVAD support was determined by quantitative polymerase chain reaction. Immunohistochemistry (IHC) and IHC-double staining was used in biopsy specimens from 32 patients before and after LVAD support to localize the BNP protein expression in the heart.
  
  
  RESULTS
  BNP plasma levels significantly decreased from 1,872 +/- 1,098 pg/ml before implantation to 117 +/- 91 pg/ml at 3 months after LVAD implantation. This decrease in plasma levels was accompanied by a significant decrease in mRNA expression (relative quantity) in the heart. IHC and IHC-double staining showed BNP immunoreactivity in the cardiomyocytes, endothelial cells, infiltrating T cells, and macrophages.
  
  
  CONCLUSIONS
  The significant decrease in serum BNP concentration after LVAD support coincides with a decrease in BNP mRNA and protein expression in the heart. BNP is produced in the left ventricle not only by cardiomyocytes but also by endothelial cells, T cells, and macrophages. Unloading of the left ventricle by a LVAD results in decreased BNP expression in the heart and plasma and may play an important role in the reverse remodeling process of the heart.
authors.affiliation: Department of Pathology, University Medical Center, Utrecht, The Netherlands. a.h.bruggink@lab.azu.nl
authors.forename: Annette H
authors.initials: AH
authors.lastname: Bruggink
authors.forename: Nicolaas
authors.initials: N
authors.lastname: de Jonge
authors.forename: Matthijs F M
authors.initials: MF
authors.lastname: van Oosterhout
authors.forename: Dick F
authors.initials: DF
authors.lastname: Van Wichen
authors.forename: Erica
authors.initials: E
authors.lastname: de Koning
authors.forename: Jaap R
authors.initials: JR
authors.lastname: Lahpor
authors.forename: Hans
authors.initials: H
authors.lastname: Kemperman
authors.forename: Frits H J
authors.initials: FH
authors.lastname: Gmelig-Meyling
authors.forename: Roel A
authors.initials: RA
authors.lastname: de Weger
mesh_terms: D000328:Adult; D001706:Biopsy; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D006352:Heart Ventricles / Q000737:chemistry / Q000503:physiopathology*; D006353:Heart-Assist Devices; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020097:Natriuretic Peptide, Brain; D017493:Leukocyte Common Antigens