Physiological or pathological--a role for relaxin in the cardiovascular system?

The omnipresent 6kDa polypeptide relaxin (RLX) is emerging as a multi-functional endocrine and paracrine factor, with a broad range of target tissues that includes the cardiovascular system. Humans and other higher primates have three RLX genes, designated H1, H2 and H3, of which H2 RLX is the major stored and circulating form. Rodents have only two RLX genes: relaxin-1 (equivalent to H2 RLX) and relaxin-3 (equivalent to H3 RLX). The recent cloning of the human RLX receptor (LGR7), a member of the leucine-rich repeat family of G-protein-coupled orphan receptors, and detection of LGR7 gene transcripts in the heart confirm this organ as a target for RLX (H2). However, evidence for production of the ligand within the cardiovascular system is limited, and few studies have clearly identified the physiological effects of RLX on cardiac function. To add to the controversy, serum concentrations and expression of RLX in the heart are elevated in chronic heart failure patients and animal models of cardiomyopathy, implying that RLX may only be a marker for pathological cardiovascular conditions, rather than normal physiology.