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 |
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Authors: | Milting Hendrik Kassner Astrid Arusoglu Latif Meyer Helmut E Morshuis Michel Brendel Ramona Klauke Bärbel El Banayosy Aly Körfer Reiner |
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Institution: | Ruhr-Universit?t Bochum, Herz-und Diabeteszentrum NRW, Klinik für Thorax-und Kardiovaskularchirurgie, Erich und Hanna Klessmann-Institut für Kardiovaskul?re Forschung und Entwicklung, Georgstr. 11, D-32545 Bad Oeynhausen, Germany. hmilting@hdz-nrw.de |
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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. |
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Keywords: | extracellular matrix ventricular assist device mechanical unloading TGF beta1 collagen reverse remodelling |
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