期刊
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
卷 68, 期 6, 页码 639-653出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2016.04.060
关键词
amyloid-beta peptides; angiotensin receptor-neprilysin inhibitor; endopeptidases; heart failure; natriuretic peptides; renin-angiotensin system
资金
- Ministerio de Educacion y Ciencia [SAF2014-59892]
- Fundacio La Marato de TV3 [201502-30]
- Generalitat de Catalunya [SGR 2014]
- Red de Investigacion Cardiovascular-RIC [RD12/0042/0047]
- Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Plan Nacional de I+D+I [FIS PI14/01682]
- ISCIII-Sudireccion General de Evaluacion y el Fondo Europeo de Desarrollo Regional
Neprilysin is a zinc-dependent endopeptidase. It is ubiquitous in distribution and promiscuous in function, with >50 putative peptide substrates with varying levels of in vitro and/or in vivo evidence of functional relevance. In the first part of this review, we discuss the genetic, structural, substrate, and pathophysiological aspects of neprilysin. We incorporate information provided by genetically modified models, as well as pre-clinical and clinical data from investigations of synthetic neprilysin inhibitors. We next highlight the value of neprilysin as a biotarget and weigh the clinical benefits of synthetic neprilysin inhibitors, either alone or in combination with antagonists of the renin-angiotensin system. Finally, we provide evidence about soluble neprilysin as a biomarker surrogate in patients with heart failure and identify important gaps that require further research before soluble neprilysin is used clinically. In sum, neprilysin is a versatile, veteran player returning yet again to center stage after an eventful career spanning >40 years. (C) 2016 by the American College of Cardiology Foundation.
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