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European Journal of Heart Failure 2006 8(3):278-283; doi:10.1016/j.ejheart.2005.09.008
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© 2005 European Society of Cardiology

Influence of ACE-inhibition and mechanical unloading on the regulation of extracellular matrix proteins in the myocardium of heart transplantation candidates bridged by ventricular assist devices

Hendrik Miltinga,*, Astrid Kassnera, Latif Arusoglua, Helmut E. Meyerb, Michel Morshuisa, Ramona Brendela, Bärbel Klaukea, Aly El Banayosya and Reiner Körfera

a Ruhr-Universität Bochum, Herz-und Diabeteszentrum NRW, Klinik für Thorax-und Kardiovaskularchirurgie, Erich und Hanna Klessmann-Institut für Kardiovaskuläre Forschung und Entwicklung Georgstr. 11, D-32545 Bad Oeynhausen, Germany
b Medizinisches Proteom-Center (MPC), Universitätsstr. 150, D-44801 Bochum, Germany

* Corresponding author. Tel.: +49 5731 97 3510; fax: +49 5731 97 2476. E-mail address:hmilting{at}hdz-nrw.de (H.Milting).


  Abstract

Background: Whether adverse structural changes in the myocardium due to remodelling can be reversed by ventricular assist device (VAD) support in patients with end-stage heart failure is controversial.

Aims: To investigate the effect of VAD support on the extra-cellular matrix.

Methods: We analysed the collagen content in terminal failing ventricles of VAD-patients and donor hearts using 4-hydroxyproline for total collagen and real time RT-PCR for fibronectin (FN), collagen I alpha 1 (Col1A1), III alpha 1 (Col3A1) and TGF beta 1 analysis.

Results: Compared to donor hearts we found similar increases in Col1A1 and TGF beta1 but not Col3A1 and FN mRNAs, which were similar in the myocardium from patients receiving a VAD or heart transplant. However, patients receiving ACE-I during VAD-support had lower Col1A1 mRNA content at transplantation. The total collagen content was not influenced by mechanical unloading or by ACE-I medication.

Conclusion: Mechanical unloading by VAD does not reduce the collagen content of the terminal failing ventricle possibly due to increased TGF beta1 levels. However, Col1A1 production may be reduced by ACE-I medication during VAD support.

Key Words: Extracellular matrix • Ventricular assist device • Mechanical unloading • TGF beta1 • Collagen • Reverse remodelling

Received August 27, 2004; Revised September 27, 2005; Accepted September 27, 2005


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