Relaxin as a Cardiovascular Hormone: Physiology, Pathophysiology and Therapeutic Promises

Silvia      Nistri; Mario      Bigazzi; Daniele      Bani

Abstract

Relaxin is a hormone belonging to the so-called relaxin superfamily, which also includes insulin-like peptides. Relaxin is best known for its effects on the female reproductive system, which primarily include lengthening of the pubic symphysis and softening of the tissues of the birth canal, stimulating mammary and endometrial development, and maintenance of myometrial quiescence. In recent years, evidence has been accumulating that relaxin can have multiple and diverse effects on both reproductive and nonreproductive organs, tissues and cells, thus acting as a sort of ‘manager’ hormone to optimize the many physiological changes taking place during pregnancy. Among the specific relaxin targets, there are the blood vessels and the heart. In fact, relaxin is a potent vasodilatator of the systemic and coronary circulation, by a mechanism of action involving nitric oxide, and can influence cardiac beating rate. Identification of the numerous possible roles of relaxin in the pathophysiology of cardiovascular diseases, not to mention the possible therapeutical applications of relaxin, remains a difficult task. Based on the known biological effects of relaxin, it is becoming increasingly evident that the potential fields of clinical investigation of human relaxin as a cardiovascular drug could be in ischemic heart disease (acute and chronic myocardial infarction), in cardiac fibrosis, in cell transplantation for cardiac repair, and in obliterative peripheral arterial disease. Availability of the homologous human peptide, knowledge of its pharmacological, pharmacokinetic and pharmacodynamic profiles, and increasing interest of clinicians and pharmaceutical companies should synergistically act to transfer relaxin from the laboratory bench to the bedside.

Keywords: leucine-rich repeat-containing G-protein coupled, receptors, myometrium, nitric oxide, matrix metalloproteinases, ischemia, cellular cardiomyoplasty