Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Milting, H; Scholz, C; Arusoglu, L; Freitag, M; Cebulla, R; Jaquet, K; Körfer, R; V Lewinski, D; Kassner, A; Brodde, OE; Kögler, H; El Banayosy, A; Pieske, B.
Selective upregulation of beta1-adrenergic receptors and dephosphorylation of troponin I in end-stage heart failure patients supported by ventricular assist devices.
J Mol Cell Cardiol. 2006; 41(3):441-450
Doi: 10.1016/j.yjmcc.2006.04.010
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Pieske Burkert Mathias
- von Lewinski Dirk
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- Abstract:
- In terminal failing hearts, adrenergic receptors are downregulated and intracellular adrenergic signal transduction is inhibited. Mechanical circulatory support by ventricular assist devices (VAD) is used to bridge patients to heart transplantation. Mechanical unloading by VAD may induce reverse remodeling in heart transplantation (HTx) candidates. However, little is known on beta-adrenergic receptor subtype regulation and adrenergic signal transduction under VAD-support. We investigated paired myocardial samples from 16 VAD-supported patients and 9 non-failing donor hearts. We analyzed beta-adrenergic receptor subtype regulation by real-time PCR and radioligand binding and cardiac troponin I phosphorylation (by phospho-cTnI-specific antibodies). We found that the beta1-adrenergic receptor (beta1AR) is downregulated at VAD-implantation on mRNA and protein levels whereas the beta2-adrenergic receptor (beta2AR) was not. After VAD-support, beta1AR protein but not its mRNA was upregulated, whereas the degree of cTnI-phosphorylation was reduced. Upregulation of beta1AR was enhanced by beta blocking medication during VAD-support. However, in 9 out of 15 patients, beta1AR-density remained below the 0.25 percentile of donor hearts. VAD-support is associated with partial normalization of the betaAR-signal transduction pathways. This beneficial effect is related to a posttranscriptional increase in beta1AR-density.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Female -
- Gene Expression Regulation -
- Heart Diseases - metabolism
- Heart Failure - metabolism
- Heart Ventricles - pathology
- Heart-Assist Devices -
- Humans -
- Male -
- Middle Aged -
- Phosphorylation -
- Receptors, Adrenergic, beta-1 - chemistry Receptors, Adrenergic, beta-1 - metabolism
- Signal Transduction -
- Troponin I - metabolism
- Up-Regulation -
- Find related publications in this database (Keywords)
- heart failure
- reverse remodeling
- ventricular assist device
- troponin I
- beta receptor