One step forward for serelaxin as a promising therapy in cardiac fibrosis.

Abstract

See related article, pp 315–322 Cardiac fibrosis is a pathological feature common to several forms of heart disease such as myocardial infarction, cardiac arrhythmias, cardiomyopathies, and heart failure. It is characterized by the net accumulation of extracellular matrix and structural remodeling of the myocardium after myocyte death, inflammation, hypertrophy, or increased workload. Several hormones, cytokines, and growth factors activate fibroblast differentiation to myofibroblasts, which produce an excessive amount of collagens in synergic response to locally produced mediators, such as transforming growth factor (TGF)-β and angiotensin II (Ang-II). Despite the importance of cardiac fibrosis, there are currently few effective treatments to stop its progression, one of which is targeting the renin–angiotensin–aldosterone system.1 The slow progress in developing new antifibrotic therapies is attributable both to a limited understanding of the exact pathophysiological mechanism and to the nonspecific mechanisms of many antifibrotic strategies. Relaxin was discovered in 1926 and is well known as a hormone of human reproduction. It regulates hemodynamic and renal adaptation during pregnancy and acts on the pregnant female reproductive tract inducing connective tissue remodeling to facilitate birth. Relaxin is a polypeptide family including 7 members. Serelaxin is the recombinant form of human relaxin-2. It binds to the relaxin family peptide receptor 1 activating the Gαs subunit of G protein–coupled receptors and adenylyl cyclase, thus increasing cyclic adenosine monophosphate. Other signaling mechanisms such as activation of the mitogen-activated protein kinase/extracellular signal–regulated kinase 1/2 or phosphoinositide 3-kinase–Akt pathway have …