Targeting the apelin pathway as a novel therapeutic approach for cardiovascular diseases.
The apelin/apelin receptor system is widely distributed and has a dominant role in cardiovascular homeostasis and disease. The apelin gene is X-linked and is synthesized as a 77 amino acid pre-pro-peptide that is subsequently cleaved to generate a family of apelin peptides that possess similar functions but display different tissue distribution, potency and receptor binding affinity. Loss-of-function experiments using the apelin and the apelin receptor knockout mice and gain-of-function experiments using apelin peptides have delineated a well-defined role of the apelin axis in cardiovascular physiology and diseases. Activation of the apelin receptor by its cognate peptide ligand, apelin, induces a wide range of physiological effects, including vasodilation, increased myocardial contractility, angiogenesis, and balanced energy metabolism and fluid homeostasis. The apelin/apelin receptor pathway is also implicated in atherosclerosis, hypertension, coronary artery disease, heart failure, diabetes and obesity, making it a promising therapeutic target. Hence, research is expanding to develop novel therapies that inhibit degradation of endogenous apelin peptides or their analogues. Chemical synthesis of stable apelin receptor agonists aims to more efficiently enhance the activation of the apelin system. Targeting the apelin/apelin receptor axis has emerged as a novel therapeutic approach against cardiovascular diseases and an increased understanding of cardiovascular actions of the apelin system will help to develop effective interventions.
State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai, China.
Jiu-Chang
JC
Zhong
State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai, China.
Zhen-Zhou
ZZ
Zhang
Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada; Department of Physiology, University of Alberta, Edmonton, Canada.
Wang
W
Wang
Department of Chemistry, University of Alberta, Edmonton, Canada.
Shaun M K
SMK
McKinnie
Department of Chemistry, University of Alberta, Edmonton, Canada.
John C
JC
Vederas
Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada; Department of Physiology, University of Alberta, Edmonton, Canada. Electronic address: gavin.oudit@ualberta.ca.
Gavin Y
GY
Oudit
D000818:Animals; D000073861:Apelin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000075244:Apelin Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004734:Energy Metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction; D018919:Neovascularization, Physiologic; D015398:Signal Transduction
C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse
Apelin; Apelin analogue; Apelin receptor; Heart failure; Vascular disease