title: Apelin/APJ System: A Novel Therapeutic Target for Myocardial Ischemia/Reperfusion Injury.
abstract: Apelin is the endogenous ligand of the G protein-coupled receptor, APJ. Recently, researches indicate that the apelin/APJ system involves in myocardial ischemia-reperfusion injury (MIRI), which is a common pathophysiological process in patients with heart diseases and therapies. The reperfusion induces the expression of apelin and APJ receptor, which play an important role in cardioprotection of MIRI. The apelin/APJ system alleviates MIRI mainly by decreasing mitochondrial reactive oxygen species and delaying the opening of mitochondrial permeability transition pores, which induce the initiation of mitophagy. Besides, the apelin/APJ system prevents mitochondrial oxygen damage and lipid peroxidation through nitric oxide formation. The apelin/APJ system also improves MIRI through other pathways, including promoting metabolic and functional recovery, significantly increasing myocardial capillary density and arteriole formation, inhibiting endoplasmic reticulum stress-induced cell apoptosis, and maintaining integrity of cell membranes. In this review, we discuss how the mechanisms of the apelin/APJ system reverse MIRI in detail and elaborate on APJ agonists, which may be used for therapy of MIRI.
authors.affiliation: Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China , Hengyang, China .
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China , Hengyang, China .
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China , Hengyang, China .
authors.forename: Lanfang
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China , Hengyang, China .
authors.forename: Linxi
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002118:Calcium / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D017136:Ion Transport; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects; D058990:Molecular Targeted Therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; C586143:apelin 13, Pyr(1)-; D009569:Nitric Oxide; D002118:Calcium
keywords: Apelin/APJ system; Ca2+ transient; endoplasmic reticulum stress; mitophagy; myocardial ischemia-reperfusion injury