The physiologic and pathophysiologic role of stimulating growth factor ST2.

Abstract

The ST2 is a member of family of receptors of interleukin I (IL-I) and consists of two isoforms: a trans-membrane of cellular one (ST2L) and soluble or circulating one (sST2). The ST2 is a receptor of IL-33 that represents IL-I like cytokine. The IL-33 manifests its cellular functions binding receptor complex consisted of accessory protein ST2L and IL-IR. The system IL-33/ST2 is activated in cardiomyocytes and fibroblasts in response to mechanical irritation or damage. It was demonstrated that interaction between IL-33 and ST2L is a cardioprotective one. The experimental models were used to demonstrate decreasing of myocardium fibrosis, prevention of development of hypertrophy of cardiomyocytes, decreasing of apoptosis and amelioration of functional capacity of myocardium at interaction of IL-33 and ST2L. In particular, the positive effects of IL-33 are related to receptor of ST2L. In turn, sST2 by binding with IL-33 sets blocking of interaction between IL-33/ST2L hence eliminating cardioprotective effects. During last years, the knowledge about the role of ST2 in pathophysiology of cardio-vascular diseases broadened and now the role of ST2 is related to myocardium dysfunction, fibrosis and remodeling. The system IL-33/ST2L, besides its myocardial role, can play an additional role in development and progressing of atherosclerosis. The system IL-33/ST2L can have a therapeutic potential in case of myocardial overload or trauma. On the contrary, sST2 acts as a false receptor of IL-33 blocking cardioprotective effects of interaction of IL-33/ST2L.