Relevance of Neutrophil Neprilysin in Heart Failure

Significant expression of neprilysin (NEP) is found on neutrophils, which present the transmembrane integer form of the enzyme. This study aimed to investigate the relationship of neutrophil transmembrane neprilysin (mNEP) with disease severity, adverse remodeling, and outcome in HFrEF. In total, 22...

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Autores principales:	Suriya Prausmüller, Georg Spinka, Henrike Arfsten, Stefanie Stasek, Rene Rettl, Philipp Emanuel Bartko, Georg Goliasch, Guido Strunk, Julia Riebandt, Julia Mascherbauer, Diana Bonderman, Christian Hengstenberg, Martin Hülsmann, Noemi Pavo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	heart failure biomarker neprilysin CD10 neutrophils Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/36507e49df39452d834ba8a98a43da2d
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spelling	oai:doaj.org-article:36507e49df39452d834ba8a98a43da2d2021-11-25T17:08:58ZRelevance of Neutrophil Neprilysin in Heart Failure10.3390/cells101129222073-4409https://doaj.org/article/36507e49df39452d834ba8a98a43da2d2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2922https://doaj.org/toc/2073-4409Significant expression of neprilysin (NEP) is found on neutrophils, which present the transmembrane integer form of the enzyme. This study aimed to investigate the relationship of neutrophil transmembrane neprilysin (mNEP) with disease severity, adverse remodeling, and outcome in HFrEF. In total, 228 HFrEF, 30 HFpEF patients, and 43 controls were enrolled. Neutrophil mNEP was measured by flow-cytometry. NEP activity in plasma and blood cells was determined for a subset of HFrEF patients using mass-spectrometry. Heart failure (HF) was characterized by reduced neutrophil mNEP compared to controls (<i>p</i> < 0.01). NEP activity on peripheral blood cells was almost 4-fold higher compared to plasma NEP activity (<i>p</i> = 0.031) and correlated with neutrophil mNEP (<i>p</i> = 0.006). Lower neutrophil mNEP was associated with increasing disease severity and markers of adverse remodeling. Higher neutrophil mNEP was associated with reduced risk for mortality, total cardiovascular hospitalizations, and the composite endpoint of both (<i>p</i> < 0.01 for all). This is the first report describing a significant role of neutrophil mNEP in HFrEF. The biological relevance of neutrophil mNEP and exact effects of angiotensin-converting-enzyme inhibitors (ARNi) at the neutrophil site have to be determined. However, the results may suggest early initiation of ARNi already in less severe HF disease, where effects of NEP inhibition may be more pronounced.Suriya PrausmüllerGeorg SpinkaHenrike ArfstenStefanie StasekRene RettlPhilipp Emanuel BartkoGeorg GoliaschGuido StrunkJulia RiebandtJulia MascherbauerDiana BondermanChristian HengstenbergMartin HülsmannNoemi PavoMDPI AGarticleheart failurebiomarkerneprilysinCD10neutrophilsBiology (General)QH301-705.5ENCells, Vol 10, Iss 2922, p 2922 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	heart failure biomarker neprilysin CD10 neutrophils Biology (General) QH301-705.5
spellingShingle	heart failure biomarker neprilysin CD10 neutrophils Biology (General) QH301-705.5 Suriya Prausmüller Georg Spinka Henrike Arfsten Stefanie Stasek Rene Rettl Philipp Emanuel Bartko Georg Goliasch Guido Strunk Julia Riebandt Julia Mascherbauer Diana Bonderman Christian Hengstenberg Martin Hülsmann Noemi Pavo Relevance of Neutrophil Neprilysin in Heart Failure
description	Significant expression of neprilysin (NEP) is found on neutrophils, which present the transmembrane integer form of the enzyme. This study aimed to investigate the relationship of neutrophil transmembrane neprilysin (mNEP) with disease severity, adverse remodeling, and outcome in HFrEF. In total, 228 HFrEF, 30 HFpEF patients, and 43 controls were enrolled. Neutrophil mNEP was measured by flow-cytometry. NEP activity in plasma and blood cells was determined for a subset of HFrEF patients using mass-spectrometry. Heart failure (HF) was characterized by reduced neutrophil mNEP compared to controls (<i>p</i> < 0.01). NEP activity on peripheral blood cells was almost 4-fold higher compared to plasma NEP activity (<i>p</i> = 0.031) and correlated with neutrophil mNEP (<i>p</i> = 0.006). Lower neutrophil mNEP was associated with increasing disease severity and markers of adverse remodeling. Higher neutrophil mNEP was associated with reduced risk for mortality, total cardiovascular hospitalizations, and the composite endpoint of both (<i>p</i> < 0.01 for all). This is the first report describing a significant role of neutrophil mNEP in HFrEF. The biological relevance of neutrophil mNEP and exact effects of angiotensin-converting-enzyme inhibitors (ARNi) at the neutrophil site have to be determined. However, the results may suggest early initiation of ARNi already in less severe HF disease, where effects of NEP inhibition may be more pronounced.
format	article
author	Suriya Prausmüller Georg Spinka Henrike Arfsten Stefanie Stasek Rene Rettl Philipp Emanuel Bartko Georg Goliasch Guido Strunk Julia Riebandt Julia Mascherbauer Diana Bonderman Christian Hengstenberg Martin Hülsmann Noemi Pavo
author_facet	Suriya Prausmüller Georg Spinka Henrike Arfsten Stefanie Stasek Rene Rettl Philipp Emanuel Bartko Georg Goliasch Guido Strunk Julia Riebandt Julia Mascherbauer Diana Bonderman Christian Hengstenberg Martin Hülsmann Noemi Pavo
author_sort	Suriya Prausmüller
title	Relevance of Neutrophil Neprilysin in Heart Failure
title_short	Relevance of Neutrophil Neprilysin in Heart Failure
title_full	Relevance of Neutrophil Neprilysin in Heart Failure
title_fullStr	Relevance of Neutrophil Neprilysin in Heart Failure
title_full_unstemmed	Relevance of Neutrophil Neprilysin in Heart Failure
title_sort	relevance of neutrophil neprilysin in heart failure
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/36507e49df39452d834ba8a98a43da2d
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_version_	1718412640725762048

Relevance of Neutrophil Neprilysin in Heart Failure

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