Relaxin-2 as New Therapeutic Alternative for Patients with Chronic Heart Failure? Role of Systemic and Local Expression Profile

Objective: Relaxin-2 is a vasoactive peptide hormone which is best known for its physiological role during pregnancy in the growth and differentiation of the reproductive tract as well as in the renal and systemic hemodynamic changes. Relaxin-2 has been postulated as a new player in human heart failure with potential diagnostic and therapeutic relevance. Clinical trials on acute heart failure patients have shown that Serelaxin treatment, a recombinant form of human relaxin-2, is safe, well tolerated and improves clinical outcome. The role of relaxin-2 in chronic heart failure has not been detailed investigated yet. Thus we analyzed samples of chronic heart failure patients on relaxin-2 and mechanistically related factors MMP-9 and iNOS.

Methods: For the analysis of the expression of relaxin-2, MMP-9 and iNOS two groups of patients were defined. Patients suffering from chronic heart failure 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). 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 with the control group (ctr 26.49 ± 1.37% versus CHF 31.35 ± 0.61%). Consistently, MMP-9 as well as iNOS were significantly higher expressed in the CHF group compared with controls (MMP-9: ctr 54.65 ± 0.78 versus CHF 66.37 ± 1.70%, iNOS: ctr 45.81 ± 1.47% versus 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 with controls were observed by trend (ctr 15.32 ± 0.11pg/ml versus CHF 19.41 ± 3.78pg/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 chronic heart failure. 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 expression in our patients collective. Modulation of Relaxin-2 may be considered as a therapeutic alternative in patients with CHF.