NR4A nuclear receptors in cardiac remodeling and neurohormonal regulation

Heart failure is characterized by the constant interplay between the underlying cardiac insult, degree of myocardial dysfunction and the activity of compensatory neurohormonal mechanisms. The sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) become activated to maintain cardiac output; however, their chronic hyperactivity will eventually become deleterious. Several nuclear hormone receptors, including the mineralocorticoid receptor and estrogen receptor, are well-known to modulate cardiac disease. Recently, the subfamily of NR4A nuclear receptors i.e. Nur77, Nurr1 and NOR-1, are emerging as key players in cardiac stress responses, as well as pivotal regulators of neurohormonal mechanisms. In this review, we summarize current literature on NR4A nuclear receptors in the heart and in various components of the SNS, RAAS and immune system and discuss the functional implications for NR4As in cardiac function and disease.