Decreased myocardial chromogranin a expression and colocalization with brain natriuretic peptide during reverse cardiac remodeling after ventricular unloading.
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.
Wohlschlaeger
Jeremias
J
Department of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Germany.
von Winterfeld
Moritz
M
Milting
Hendrik
H
El Banayosy
Aly
A
Schmitz
Klaus Jürgen
KJ
Takeda
Atsushi
A
Takeda
Nobuakira
N
Azhari
Petra
P
Schmid
Christof
C
August
Christian
C
Schmid
Kurt Werner
KW
Baba
Hideo Andreas
HA
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
D019002:CD56 Antigen; D053379:Chromogranin A; D019006:Neural Cell Adhesion Molecules; D020097:Natriuretic Peptide, Brain