Details

Autor(en) / Beteiligte

• Zhong, Jiu-Chang
• Zhang, Zhen-Zhou
• Wang, Wang
• McKinnie, Shaun M.K.
• Vederas, John C.
• Oudit, Gavin Y.

Titel

Targeting the apelin pathway as a novel therapeutic approach for cardiovascular diseases

Ist Teil von

• Biochimica et biophysica acta. Molecular basis of disease, 2017-08, Vol.1863 (8), p.1942-1950

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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. The apelin/apelin receptor system plays a dominant role in cardiovascular homeostasis and diseases. Activation of the apelin receptor by apelin, apelin agonists, apelin analogues and Elabela/Toddler induces a wide range of physiological effects, including vasodilation, increased myocardial contractility, improved vascular function and fluid homeostasis. The apelin pathway is also implicated in atherosclerosis, hypertension, coronary artery disease, pulmonary arterial hypertension, heart failure and atherosclerosis, making it a promising therapeutic target. RAS, renin-angiotensin system; PAH, pulmonary arterial hypertension; PASMC, pulmonary arterial smooth muscle cell; VSMC, vascular smooth muscle cell; EC, endothelial cell; NO, nitric oxide; eNOS, endothelial nitric oxide synthase. [Display omitted] •Apelin peptides, pyr-apelin 13 and apelin 17, are highly conserved in mammals.•Apelin is protective against heart diseases.•Apelin is protective against vascular diseases.•ACE2 and NEP are two enzymes that degrades apelin peptides.•Apelin analogs represents new therapeutic agents for cardiovascular diseases.