A Test in Context: Neprilysin: Function, Inhibition, and Biomarker.

Antoni Bayes-Genis, Jaume Barallat, A Mark Richards

Journal: Journal of the American College of Cardiology 2017;68(6):639-653

PMID: 27491909

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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.

Address: 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: [email protected].; Biochemistry Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.; 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.

DOI: 10.1016/j.jacc.2016.04.060