Ramipril Reduces Acylcarnitines and Distinctly Increases Angiotensin-Converting Enzyme 2 Expression in Lungs of Rats

The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is abundantly expressed in many organs. With respect to the role of circulating ACE2 and its receptor expression in the pathogenesis...

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Main Authors: Joanna Kosacka, Claudia Berger, Uta Ceglarek, Anne Hoffmann, Matthias Blüher, Nora Klöting
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/12/4/293
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author Joanna Kosacka
Claudia Berger
Uta Ceglarek
Anne Hoffmann
Matthias Blüher
Nora Klöting
author_facet Joanna Kosacka
Claudia Berger
Uta Ceglarek
Anne Hoffmann
Matthias Blüher
Nora Klöting
author_sort Joanna Kosacka
collection DOAJ
description The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is abundantly expressed in many organs. With respect to the role of circulating ACE2 and its receptor expression in the pathogenesis of the SARS-CoV-2 infection, it is still debated whether diseases such as hypertension or pharmacotherapies, including ACE inhibitors and angiotensin receptor blockers that affect ACE2 receptor expression, may modulate the severity and outcome of the coronavirus disease 2019 (COVID-19). We therefore tested the hypothesis that treatment with the ACE inhibitor Ramipril affects organ-specific ACE2 receptor mRNA and protein expression as well as the serum metabolome in BioBreeding (BB) rats. Twelve male BioBreeding rats were randomly divided into a Ramipril (10 mg/kg body weight) treatment group or a control group (<i>N</i> = 12; <i>n</i> = 6 per group) over a period of seven days. Ramipril treatment resulted in the reduction of acylcarnitines (C3–C6) out of 64 metabolites. Among the different organs studied, only in the lungs did Ramipril treatment significantly increase both <i>Ace2</i> mRNA and ACE2 receptor membrane protein levels. Increased ACE2 receptor lung expression after Ramipril treatment was not associated with differences in ACE2 serum concentrations between experimental groups. Our data provide experimental in vivo evidence that the ACE inhibitor Ramipril selectively increases pulmonary ACE2 receptor mRNA and protein levels and reduces acylcarnitines.
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spelling doaj.art-648c5212a2bf4966888cc25a9e60f45c2023-11-30T21:31:51ZengMDPI AGMetabolites2218-19892022-03-0112429310.3390/metabo12040293Ramipril Reduces Acylcarnitines and Distinctly Increases Angiotensin-Converting Enzyme 2 Expression in Lungs of RatsJoanna Kosacka0Claudia Berger1Uta Ceglarek2Anne Hoffmann3Matthias Blüher4Nora Klöting5Medical Department III—Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Liebigstr. 20, 04103 Leipzig, GermanyMedical Department III—Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Liebigstr. 20, 04103 Leipzig, GermanyInstitute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University Medical Center, 04103 Leipzig, GermanyHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Ph.-Rosenthal-Str. 27, 04103 Leipzig, GermanyMedical Department III—Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Liebigstr. 20, 04103 Leipzig, GermanyHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Ph.-Rosenthal-Str. 27, 04103 Leipzig, GermanyThe angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is abundantly expressed in many organs. With respect to the role of circulating ACE2 and its receptor expression in the pathogenesis of the SARS-CoV-2 infection, it is still debated whether diseases such as hypertension or pharmacotherapies, including ACE inhibitors and angiotensin receptor blockers that affect ACE2 receptor expression, may modulate the severity and outcome of the coronavirus disease 2019 (COVID-19). We therefore tested the hypothesis that treatment with the ACE inhibitor Ramipril affects organ-specific ACE2 receptor mRNA and protein expression as well as the serum metabolome in BioBreeding (BB) rats. Twelve male BioBreeding rats were randomly divided into a Ramipril (10 mg/kg body weight) treatment group or a control group (<i>N</i> = 12; <i>n</i> = 6 per group) over a period of seven days. Ramipril treatment resulted in the reduction of acylcarnitines (C3–C6) out of 64 metabolites. Among the different organs studied, only in the lungs did Ramipril treatment significantly increase both <i>Ace2</i> mRNA and ACE2 receptor membrane protein levels. Increased ACE2 receptor lung expression after Ramipril treatment was not associated with differences in ACE2 serum concentrations between experimental groups. Our data provide experimental in vivo evidence that the ACE inhibitor Ramipril selectively increases pulmonary ACE2 receptor mRNA and protein levels and reduces acylcarnitines.https://www.mdpi.com/2218-1989/12/4/293ACE2lungsRamiprilSARS-CoV-2C3MC4M
spellingShingle Joanna Kosacka
Claudia Berger
Uta Ceglarek
Anne Hoffmann
Matthias Blüher
Nora Klöting
Ramipril Reduces Acylcarnitines and Distinctly Increases Angiotensin-Converting Enzyme 2 Expression in Lungs of Rats
Metabolites
ACE2
lungs
Ramipril
SARS-CoV-2
C3M
C4M
title Ramipril Reduces Acylcarnitines and Distinctly Increases Angiotensin-Converting Enzyme 2 Expression in Lungs of Rats
title_full Ramipril Reduces Acylcarnitines and Distinctly Increases Angiotensin-Converting Enzyme 2 Expression in Lungs of Rats
title_fullStr Ramipril Reduces Acylcarnitines and Distinctly Increases Angiotensin-Converting Enzyme 2 Expression in Lungs of Rats
title_full_unstemmed Ramipril Reduces Acylcarnitines and Distinctly Increases Angiotensin-Converting Enzyme 2 Expression in Lungs of Rats
title_short Ramipril Reduces Acylcarnitines and Distinctly Increases Angiotensin-Converting Enzyme 2 Expression in Lungs of Rats
title_sort ramipril reduces acylcarnitines and distinctly increases angiotensin converting enzyme 2 expression in lungs of rats
topic ACE2
lungs
Ramipril
SARS-CoV-2
C3M
C4M
url https://www.mdpi.com/2218-1989/12/4/293
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