‘Relaxin’ the stiffened heart and arteries: The therapeutic potential for relaxin in the treatment of cardiovascular disease

Although originally characterised as a reproductive hormone, relaxin has emerged as a multi-functional endocrine and paracrine factor that plays a number of important roles in several organs, including the normal and diseased cardiovascular system. The recent discovery of the H3/relaxin-3 gene, and the elusive receptors for relaxin (Relaxin family peptide receptor; RXFP1) and relaxin-3 (RXFP3/RXFP4) have led to the re-classification of a distinct relaxin peptide/receptor family. Additionally, the identification of relaxin and RXFP1 mRNA and/or relaxin binding sites in the heart and blood vessels has confirmed that the cardiovascular system is a target for relaxin peptides. While evidence for the production of relaxins within the cardiovascular system is limited, several studies have established that the relaxin genes are upregulated in the diseased human and rodent heart where they likely act as cardioprotective agents. The ability of relaxin to protect the heart is most likely mediated via its antifibrotic, anti-hypertrophic, anti-inflammatory and vasodilatory actions, but it may also directly stimulate myocardial regeneration and repair. This review describes relaxin and its primary receptor (RXFP1) in relation to the roles and effects of relaxin in the normal and pathological cardiovascular system. It is becoming increasingly clear that relaxin has a number of diverse physiological and pathological roles in the cardiovascular system that may have important therapeutic and clinical implications.