Decreased Myocardial Chromogranin A Expression and Colocalization With Brain Natriuretic Peptide During Reverse Cardiac Remodeling After Ventricular Unloading

Wohlschlaeger, Jeremias; von Winterfeld, Moritz; Milting, Hendrik; El Banayosy, Aly; Schmitz, Klaus Jürgen; Takeda, Atsushi; Takeda, Nobuakira; Azhari, Petra; Schmid, Christof; August, Christian; Schmid, Kurt Werner; Baba, Hideo Andreas

doi:10.1016/j.healun.2008.01.017

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 27, Issue 4 , Pages 442-449, April 2008

Decreased Myocardial Chromogranin A Expression and Colocalization With Brain Natriuretic Peptide During Reverse Cardiac Remodeling After Ventricular Unloading

Jeremias Wohlschlaeger, MD
- Department of Pathology and Neuropathology University Hospital Essen, University of Duisburg-Essen, Germany
Moritz von Winterfeld
- Department of Pathology and Neuropathology University Hospital Essen, University of Duisburg-Essen, Germany
Hendrik Milting, PhD
- Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie, Erich und Hanna Klessmann-Institut für Kardiovaskuläre Forschung und Entwicklung, Bad Oeynhausen, Germany
Aly El Banayosy, MD
- Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie, Erich und Hanna Klessmann-Institut für Kardiovaskuläre Forschung und Entwicklung, Bad Oeynhausen, Germany
Klaus Jürgen Schmitz, MD
- Department of Pathology and Neuropathology University Hospital Essen, University of Duisburg-Essen, Germany
Atsushi Takeda, MD
- Faculty of Health Science, School of Physical Therapy, Gumma Paz College, Gumma, Japan
Nobuakira Takeda, MD
- Department of Internal Medicine, Jikei University, Tokyo, Japan
Petra Azhari, MD
- Department of Thoracic and Cardiovascular Surgery, University Hospital Essen, Germany
Christof Schmid, MD
- Department of Thoracic and Cardiovascular Surgery, University of Regensburg, Germany
Christian August, MD
- Department of Pathology, University Hospital Münster, Germany.
Kurt Werner Schmid, MD
- Department of Pathology and Neuropathology University Hospital Essen, University of Duisburg-Essen, Germany
Hideo Andreas Baba, MD
- Department of Pathology and Neuropathology University Hospital Essen, University of Duisburg-Essen, Germany
- Reprint requests: Univ.-Prof. Dr. med. H. A. Baba, Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. Telephone: 0049-201-723-3577. Fax: 0049-201-723-3378.

Received 4 October 2007; received in revised form 10 January 2008; accepted 12 January 2008.

Aims

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.