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.


OBJECTIVE
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.


CONCLUSIONS
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.
Milting
Hendrik
H
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. hmilting@hdz-nrw.de
Kassner
Astrid
A
Arusoglu
Latif
L
Meyer
Helmut E
HE
Morshuis
Michel
M
Brendel
Ramona
R
Klauke
Bärbel
B
El Banayosy
Aly
A
Körfer
Reiner
R
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002648:Child; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D006801:Humans; D008875:Middle Aged; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
D000806:Angiotensin-Converting Enzyme Inhibitors; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1