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

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.