Transcriptional evaluation of relaxin and endothelin-1 axis in heart failure patients: First evidence of its involvement during left ventricular assist device support.
BACKGROUND
Left ventricular assist devices (LVAD) are implanted in patients with end-stage heart failure (ESHF) as a mechanical support for the failing myocardium, which is characterized by an activation of the neuro-hormonal system, with release of vasoactive mediators, such as endothelin (ET)-1 and relaxin (RLX)-2. The aim of this study was to evaluate whether LVAD is able to modulate the RLX-2 and ET-1 system expression in ESHF patients.


METHODS
Cardiac tissue was collected from ESHF patients before LVAD implantation (pre-LVAD group, n = 22), at the time of cardiac transplantation with concomitant LVAD removal (post-LVAD group, n = 6), and from stable HF patients on medical therapy at the time of cardiac transplantation (HTx group, n = 7). The expression of RLX-2, ET-1 system and inflammatory markers (IL-8, IL-6, TNF-α) were evaluated by Real-Time PCR.


RESULTS
RLX-2 mRNA resulted similar in pre-LVAD and HTx, but it was significantly increased in post-LVAD (p = 0.02/p = 0.01 respectively). A similar trend was observed for ET-1 and ET-converting enzyme (ECE)-1 while no significant difference was observed for ET-receptors. A positive correlation was found between ET-1 and ET-A (p = 0.031) and ECE-1 (p < 0.0001). The inflammatory markers resulted activated in all the three groups. A significant correlation between RLX-2 and ET-1 in pre-LVAD, as well as between RLX-2 and IL-8/IL-6, was found.


CONCLUSIONS
Our research investigates for the first time the involvement of RLX-2 and ET-1 system in ESHF patients supported by LVAD, demonstrating their potential ability to partially recover the failing myocardium, indicating their possible clinical role as biomarkers or pharmacological agents in LVAD patients.


TRANSLATIONAL ASPECT
The study of novel biomarkers in patients supported by continuous axial flow devices may be a starting point analysis applicable to patients with centrifugal flow devices.
['Cabiati|Manuela|M|', 'Botta|Luca|L|', 'Caselli|Chiara|C|', 'Del Ry|Silvia|S|']
D019332:Endothelin-1 D006333:Heart Failure D016027:Heart Transplantation D006353:Heart-Assist Devices D006801:Humans D012065:Relaxin
RLX-2 ET-1 system Inflammatory markers Real-Time PCR Mechanical circulatory support