title: Decreased myocardial chromogranin a expression and colocalization with brain natriuretic peptide during reverse cardiac remodeling after ventricular unloading.
abstract: OBJECTIVE
  In chronic heart failure, atrial and brain natriuretic peptide expression is increased and serves as a clinical marker of cardiac hypertrophy. Chromogranin A is also up-regulated during chronic heart failure and associated with disease severity and prognosis. Significant decrease of both natriuretic peptide and hypertrophy after left ventricular assist device (LVAD) treatment was reported. This study investigated whether chromogranin A and neural cell adhesion molecule (NCAM)/CD56 are associated with cardiac hypertrophy and regulated by LVAD.
  
  
  METHODS
  Expression of atrial and brain natriuretic peptide, chromogranin A, and NCAM/CD56 were investigated by immunohistochemistry and morphometrically quantified in 33 paired myocardial samples before and after LVAD. In a different set of patients, chromogranin A was evaluated in the plasma. Cardiomyocyte colocalization of brain natriuretic peptide and chromogranin A was visualized by immunofluorescence doublestaining.
  
  
  RESULTS
  Natriuretic peptide and chromogranin A protein expression is significantly decreased after LVAD (p < 0.05). NCAM/CD56 expression remains unaltered by unloading. In contrast with natriuretic peptide, chromogranin A and NCAM/CD56 expression is not correlated with cardiomyocyte diameters. Although increased compared with controls, no significant differences for chromogranin A plasma levels were found before and after LVAD. Sarcoplasmic colocalization of chromogranin A and brain natriuretic peptide is considerably decreased after LVAD.
  
  
  CONCLUSIONS
  Neither chromogranin A nor CD56 is associated with cardiac hypertrophy. Chromogranin A is significantly decreased by ventricular support. Sarcoplasmic colocalization of brain natriuretic peptide and chromogranin A is diminished after unloading. However, owing to its low expression, the negative regulation of chromogranin A is not reflected by plasma levels and thus does not appear to be an appropriate biomarker of reverse cardiac remodeling after unloading.
authors: Department of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors: Jeremias
authors: J
authors: Wohlschlaeger
authors: Moritz
authors: M
authors: von Winterfeld
authors: Hendrik
authors: H
authors: Milting
authors: Aly
authors: A
authors: El Banayosy
authors: Klaus Jürgen
authors: KJ
authors: Schmitz
authors: Atsushi
authors: A
authors: Takeda
authors: Nobuakira
authors: N
authors: Takeda
authors: Petra
authors: P
authors: Azhari
authors: Christof
authors: C
authors: Schmid
authors: Christian
authors: C
authors: August
authors: Kurt Werner
authors: KW
authors: Schmid
authors: Hideo Andreas
authors: HA
authors: Baba
mesh_terms: D000293:Adolescent; D000328:Adult; D019002:CD56 Antigen / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D053379:Chromogranin A / Q000378:metabolism; D002908:Chronic Disease; D015536:Down-Regulation; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D006353:Heart-Assist Devices; D006801:Humans; D006984:Hypertrophy; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014018:Tissue Distribution; D020257:Ventricular Remodeling
chemical_list: D019002:CD56 Antigen; D053379:Chromogranin A; D019006:Neural Cell Adhesion Molecules; D020097:Natriuretic Peptide, Brain