Purpose: Relaxin-2 is a vasoactive peptide hormone known for its physiological role during pregnancy. Relaxin-2 has been proposed to have diagnostic and therapeutic relevance in patients with chronic heart failure (CHF). Clinical trials on acute heart failure patients have shown that Serelaxin treatment, a recombinant human relaxin-2, is safe, well tolerated and improves clinical outcome. Our aim was to investigate the local and systemic expression profiles of Relaxin-2 and related molecules (iNOS, and MMP-9) in patients with end-stage CHF. Methods: Patients suffering from CHF undergoing heart transplantation or LVAD implantation were included into the chronic heart failure group (CHF; n= 7) and healthy myocardial tissue and blood samples from by-pass surgery patients with EF> 65% served as controls (ctr; n= 5). We analyzed the local and systemic expression of relaxin-2, MMP-9 and iNOS after informed consent. Myocardial tissue samples and blood samples of the patients were analyzed via immunohistochemical staining and ELISA analysis, respectively. Results are expressed as mean±SEM, whereas p< 0.05 was considered as statistically significant. Results: A significant higher protein expression level of relaxin-2 was detected in the CHF myocardial tissue compared to the control group (ctr 26.49±1.37% vs. CHF 31.35±0.61%). Consistently, MMP-9 as well as iNOS were significantly higher expressed in the CHF group compared to controls (MMP-9: ctr 54.65±0.78 vs. CHF 66.37±1.70%, iNOS: ctr 45.81±1.47% vs. CHF 50.62±1.57%). The circulating levels of Relaxin-2 did not differ significantly between both groups. However, higher Relaxin-2 levels in the CHF group compared to controls were observed by trend (ctr 15.32±0.11 pg/ ml vs. CHF 19.41±3.78 pg/ml). Conclusion: Previous studies appointed relaxin-2 as new promising drug to treat patients with acute heart failure. Our study shows a modulated expression profile of relaxin-2 in patients suffering from end-stage CHF. Additionally, MMP-9, postulated to mediate its extracellular matrix turnover via relaxin-2 signaling, and iNOS, known to be induced by relaxin-2, are differently expressed in our patients collective. Modulation of Relaxin-2 may be considered as a therapeutic alternative in patients with CHF.(
451)Clinical Genetics in Cardio-Oncology
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