期刊
TRENDS IN PHARMACOLOGICAL SCIENCES
卷 36, 期 9, 页码 560-567出版社
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2015.06.002
关键词
apelin; Elabela/Toddler; pulmonary arterial hypertension; apelin receptor; APJ; biased agonist
资金
- Wellcome Trust [085686]
- Metabolic and Cardiovascular Disease [096822/Z/11/Z]
- British Heart Foundation [PG/09/050/27734]
- Medical research Council (MRC)
- National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre
- Medical Research Council [MC_PC_12012] Funding Source: researchfish
- MRC [MC_PC_12012] Funding Source: UKRI
Apelin and its G protein-coupled receptor (GPCR) have emerged as a key signalling pathway in the cardiovascular system. The peptide is a potent inotropic agent and vasodilator. Remarkably, a peptide, Elabela/Toddler, that has little sequence similarity to apelin, has been proposed as a second endogenous apelin receptor ligand and is encoded by a gene from a region of the genome previously classified as 'non-coding'. Apelin is downregulated in pulmonary arterial hypertension and heart failure. To replace the missing endogenous peptide, 'biased' apelin agonists have been designed that preferentially activate G protein pathways, resulting in reduced beta-arrestin recruitment and receptor internalisation, with the additional benefit of attenuating detrimental beta-arrestin signalling. Proof-of-concept studies support the clinical potential for apelin receptor biased agonists.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据