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The effects of angiotensin receptor neprilysin inhibition by sacubitril/valsartan on adipose tissue transcriptome and Protein expression in obese hypertensive patients

Stinkens, R. and van der Kolk, B.W. and Jordan, J. and Jax, T. and Engeli, S. and Heise, T. and Jocken, J. W. and May, M. and Schindler, C. and Havekes, B. and Schaper, N. and Albrecht, D. and Kaiser, S. and Hartmann, N. and Letzkus, M. and Langenickel, T.H. and Goossens, G.H. and Blaak, E.E. (2018) The effects of angiotensin receptor neprilysin inhibition by sacubitril/valsartan on adipose tissue transcriptome and Protein expression in obese hypertensive patients. Scientific Reports, 8 (3933), pp. 1-7. Nature Publishing Group. DOI: 10.1038/s41598-018-22194-z ISSN 2045-2322

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Official URL: https://www.nature.com/articles/s41598-018-22194-z

Abstract

Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients. Abdominal subcutaneous AT biopsies were collected before and after intervention to determine the AT transcriptome and expression of proteins involved in lipolysis, NP signaling and mitochondrial oxidative metabolism. Both sacubitril/valsartan and amlodipine treatment did not significantly induce AT transcriptional changes in pathways related to lipolysis, NP signaling and oxidative metabolism. Furthermore, protein expression of adipose triglyceride lipase (ATGL) (Ptime*group = 0.195), hormone-sensitive lipase (HSL) (Ptime*group = 0.458), HSL-ser660 phosphorylation (Ptime*group = 0.340), NP receptor-A (NPRA) (Ptime*group = 0.829) and OXPHOS complexes (Ptime*group = 0.964) remained unchanged. In conclusion, sacubitril/valsartan treatment for 8 weeks did not alter the abdominal subcutaneous AT transcriptome and expression of proteins involved in lipolysis, NP signaling and oxidative metabolism in obese hypertensive patients.

Item URL in elib:https://elib.dlr.de/125375/
Document Type:Article
Title:The effects of angiotensin receptor neprilysin inhibition by sacubitril/valsartan on adipose tissue transcriptome and Protein expression in obese hypertensive patients
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Stinkens, R.Department of Human Biology, NetherlandsUNSPECIFIED
van der Kolk, B.W.Department of Human Biology, Maastricht University Medical Center, the NetherlandsUNSPECIFIED
Jordan, J.Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.UNSPECIFIED
Jax, T.Profil, GermanyUNSPECIFIED
Engeli, S.Institute of Clinical Pharmacology, Hannover Medical School, Hannover, GermanyUNSPECIFIED
Heise, T.Profil, Neuss, GermanyUNSPECIFIED
Jocken, J. W.Department of Human Biology, Maastricht University Medical Center, the NetherlandsUNSPECIFIED
May, M.Institute for Clinical Pharmacology, MHH, GermanyUNSPECIFIED
Schindler, C.Institute for Clinical Pharmacology, MHH, GermanyUNSPECIFIED
Havekes, B.Department of Internal Medicine, NetherlandsUNSPECIFIED
Schaper, N.Department of Human Biology, Maastricht University Medical Center, the NetherlandsUNSPECIFIED
Albrecht, D.Translational Medicine Novartis, SwitzerlandUNSPECIFIED
Kaiser, S.Translational Medicine, Novartis Institutes for Biomedical Research, Basel, SwitzerlandUNSPECIFIED
Hartmann, N.Translational Medicine, Novartis Institutes for Biomedical Research, Basel, SwitzerlandUNSPECIFIED
Letzkus, M.Translational Medicine, Novartis Institutes for Biomedical Research, Basel, SwitzerlandUNSPECIFIED
Langenickel, T.H.Translational Medicine, Novartis, SwitzerlandUNSPECIFIED
Goossens, G.H.Department of Human Biology, NetherlandsUNSPECIFIED
Blaak, E.E.Department of Human Biology, NetherlandsUNSPECIFIED
Date:2 March 2018
Journal or Publication Title:Scientific Reports
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:8
DOI :10.1038/s41598-018-22194-z
Page Range:pp. 1-7
Publisher:Nature Publishing Group
ISSN:2045-2322
Status:Published
Keywords:angiotensin; sacubitril/valsartan; receptor neprilysin Inhibition; hypertension; hypertensive patients; renin-angiotensin System; cardiometabolic diseases
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Systemphysiologie
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Cardiovascular Medicine in Aerospace
Deposited By: Becker, Christine
Deposited On:19 Dec 2018 09:37
Last Modified:19 Dec 2018 09:37

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