The Protective Effects and Mechanisms of Apelin/APJ System on Ischemic Stroke: A Promising Therapeutic Target

Abstract

The orphan receptor APJ and its endogenous ligand apelin, which are expressed in the brain, are the major components of the apelin/APJ system. Growing evidence shows that the apelin/APJ system plays a vital role in the pathophysiology of cerebral ischemic injury. Targeting the apelin/APJ system may have protective effects on cerebral ischemic injury. In this review, we sum up the latest research progress relating to the actions and therapeutic potential of the apelin/APJ system in ischemic stroke. An in-depth knowledge of the pathophysiological effects of the apelin/APJ system and the underlying mechanisms will help to develop novel therapeutic interventions for ischemic stroke.

Keywords: apelin/APJ system; ischemic stroke; molecular mechanisms; neuroprotection; signaling pathways.

Figure 1

Overview of apelin/APJ system–mediated signaling pathways. Canonical ligand-dependent APJ signaling via Gα_i and Gα_q leads to the activation of protein kinase C (PKC), phosphatidylinositide 3-kinase (PI3K), and nitrous oxide synthase (NOS) pathways and the inhibition of adenylyl cyclase (AC) (19). In endothelial cells, ligand activates a Gα₁₃-dependent pathway that allows the transcription of myocyte enhancer factor-2 (MEF2). Moreover, the G protein–independent pathway of the apelin/APJ system is mediated by G protein–coupled receptor kinase (GRK) and β-arrestin. Arrowheads indicate activation, and blunted arrows indicate inhibition.