- \(\bf Background\)
In terminal failing hearts ventricular assist devices (VAD) are implanted as a bridge to transplantation. Endothelin receptor (ETR) antagonists are used for treatment of secondary pulmonary hypertension in VAD patients. However, the cardiac ETR regulation in human heart failure and during VAD support is incompletely understood.
\(\bf Methods\)
In paired left ventricular samples of 12 dilated cardiomyopathy patients we investigated the density of endothelin A \((ET_{A})\) and B \((ET_{B})\) receptors before VAD implantation and after device removal. Left ventricular samples of 12 non-failing donor hearts served as control. Receptor quantification was performed by binding of \([^{125}I]\)-ET-1 in the presence of nonselective and \(ET_{A}\) selective ETR ligands as competitors. Additionally, the ETR mRNA expression was analyzed using quantitative real-time-PCR.
\(\bf Results\)
The mRNA of \(ET_{A}\) but not \(ET_{B}\) receptors was significantly elevated in heart failure, whereas total ETR density analyzed by radioligand binding was significantly reduced due to \(ET_{B}\) receptor down regulation. \(ET_{A}\) and \(ET_{B}\) receptor density showed poor correlation to mRNA data (spearman correlation factor: 0.43 and 0.31, respectively). VAD support had no significant impact on the density of both receptors and on mRNA expression of \(ET_{A}\) whereas \(ET_{A}\) mRNA increased during VAD. A meta-analysis reveals that the \(ET_{A}\) receptor regulation in human heart failure appears to depend on non-failing hearts.
\(\bf Conclusions\)
In deteriorating hearts of patients suffering from dilated cardiomyopathy the \(ET_{A}\) receptor density is not changed whereas the \(ET_{B}\) receptor is down regulated. The mRNA and the proteins of \(ET_{A}\) and \(ET_{B}\) show a weak correlation. Non-failing hearts might influence the interpretation of \(ET_{A}\) receptor regulation. Mechanical unloading of the failing hearts has no impact on the myocardial ETR density.