title: A Test in Context: Neprilysin: Function, Inhibition, and Biomarker.
abstract: 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.
authors: Cardiology Service and Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain. Electronic address: abayesgenis@gmail.com.
authors: Antoni
authors: A
authors: Bayes-Genis
authors: Biochemistry Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors: Jaume
authors: J
authors: Barallat
authors: Cardiovascular Research Institute, National University Health System, and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cardiac Department, National University Health System, Singapore; Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
authors: A Mark
authors: AM
authors: Richards
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000097:blood*; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D015415:Biomarkers; D015260:Neprilysin
keywords: amyloid-beta peptides; angiotensin receptor-neprilysin inhibitor; endopeptidases; heart failure; natriuretic peptides; renin–angiotensin system