Endothelial Derived Neuregulin-1 may be Important for Cardioprotection Induced by Ischemic Preconditioning

Abstract

Aim of review:The underlying mechanisms of ischemic preconditioning (IPC) have been studied for many years, but have not been elucidated completely. The available literatures indicate that endothelial derived neuregulin-1 (NRG-1) is involved in myocardial ischemia/reperfusion injury (IRI) and protects cardiomyocytes against H2O2-induced apoptosis by regulating endoplasmic reticulum stress (ERS). The aim of this review is to provide the evidence that endothelial derived NRG-1 maybe a crucial biomolecule mediating powerful cardioprotection by IPC. Methods: According to the available literatures, this review will first discuss the factors attributable to cardioprotection of IPC and then provide an overview of the cellular and molecular mechanisms of endothelial derived NRG-1 maybe involved in IPC induced cardioprotection. Recent findings: Multiple factors are attributable to cardioprotection induced by IPC. It has been shown that anoxia preconditioning in vitro can not provide cardioprotection as much as the IPC in vivo. During myocardial ischemic conditioning, endothelial cells may play several roles: a" receptor"for blood-borne conditioning moieties, a sensor for hypoxic stress and a paracrine organ. The NRG-1 produced by endothelial cells has been proved to protect against myocardial IRI through a PI3K/Akt pathway. Furthermore, unbalanced endoplasmic reticulum stress is one of the important mechanisms of IRI, and IPC has been demonstrated to protect myocardial IRI by regulating endoplasmic reticulum stress. In addition, NRG-1 may attenuate IRI by regulating cold inducible RNA-binding protein with its downstream endoplasmic reticulum stress related signaling pathways. Summary: Endothelial derived NRG-1 and its downstream signaling pathways are involved in multiple aspects of cardiac physiology and function, and can provide a significant protection against myocardial injury. The available evidence indicates that selective deletion of endothelial derived NRG-1 in vivo decreases the tolerance to IRI, as demonstrated by impaired recovery of post-ischemic myocardial contraction function. Thus, endothelial derived NRG-1 maybe a crucial biomolecule mediating powerful cardioprotection by IPC. If this new view is proved by basic and clinical experiments, a crucial biomolecule mediated cardioprotection induced by IPC would be revealed.