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Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation

Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damag...

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Autores principales: Betz, Iris Rosa, Qaiyumi, Sarah Julia, Goeritzer, Madeleine, Thiele, Arne, Brix, Sarah, Beyhoff, Niklas, Grune, Jana, Klopfleisch, Robert, Greulich, Franziska, Uhlenhaut, Nina Henriette, Kintscher, Ulrich, Foryst-Ludwig, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657733/
https://www.ncbi.nlm.nih.gov/pubmed/34884498
http://dx.doi.org/10.3390/ijms222312695
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author Betz, Iris Rosa
Qaiyumi, Sarah Julia
Goeritzer, Madeleine
Thiele, Arne
Brix, Sarah
Beyhoff, Niklas
Grune, Jana
Klopfleisch, Robert
Greulich, Franziska
Uhlenhaut, Nina Henriette
Kintscher, Ulrich
Foryst-Ludwig, Anna
author_facet Betz, Iris Rosa
Qaiyumi, Sarah Julia
Goeritzer, Madeleine
Thiele, Arne
Brix, Sarah
Beyhoff, Niklas
Grune, Jana
Klopfleisch, Robert
Greulich, Franziska
Uhlenhaut, Nina Henriette
Kintscher, Ulrich
Foryst-Ludwig, Anna
author_sort Betz, Iris Rosa
collection PubMed
description Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle. Afterwards, RNA sequencing was performed using an Illumina HiSeq sequencer. Confirmatory analysis was performed in PCMs and HL-1 cardiomyocytes. For an in vivo study, 129 sv mice were orally treated with a vehicle or C16:1n7 for 22 days. After 5 days of pre-treatment, the mice were injected with ISO (25 mg/kg/d s. c.) for 4 consecutive days. Cardiac phenotyping was performed using echocardiography. In total, 129 genes were differentially expressed in PCMs stimulated with C16:1n7, including Angiopoietin-like factor 4 (Angptl4) and Pyruvate Dehydrogenase Kinase 4 (Pdk4). Both Angptl4 and Pdk4 are proxisome proliferator-activated receptor α/δ (PPARα/δ) target genes. Our in vivo results indicated cardioprotective and anti-fibrotic effects of C16:1n7 application in mice. This was associated with the C16:1n7-dependent regulation of the cardiac PPAR-specific signaling pathways. In conclusion, our experiments demonstrated that C16:1n7 might have protective effects on cardiac fibrosis and inflammation. Our study may help to develop future lipid-based therapies for catecholamine-induced cardiac damage.
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spelling pubmed-86577332021-12-10 Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation Betz, Iris Rosa Qaiyumi, Sarah Julia Goeritzer, Madeleine Thiele, Arne Brix, Sarah Beyhoff, Niklas Grune, Jana Klopfleisch, Robert Greulich, Franziska Uhlenhaut, Nina Henriette Kintscher, Ulrich Foryst-Ludwig, Anna Int J Mol Sci Article Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle. Afterwards, RNA sequencing was performed using an Illumina HiSeq sequencer. Confirmatory analysis was performed in PCMs and HL-1 cardiomyocytes. For an in vivo study, 129 sv mice were orally treated with a vehicle or C16:1n7 for 22 days. After 5 days of pre-treatment, the mice were injected with ISO (25 mg/kg/d s. c.) for 4 consecutive days. Cardiac phenotyping was performed using echocardiography. In total, 129 genes were differentially expressed in PCMs stimulated with C16:1n7, including Angiopoietin-like factor 4 (Angptl4) and Pyruvate Dehydrogenase Kinase 4 (Pdk4). Both Angptl4 and Pdk4 are proxisome proliferator-activated receptor α/δ (PPARα/δ) target genes. Our in vivo results indicated cardioprotective and anti-fibrotic effects of C16:1n7 application in mice. This was associated with the C16:1n7-dependent regulation of the cardiac PPAR-specific signaling pathways. In conclusion, our experiments demonstrated that C16:1n7 might have protective effects on cardiac fibrosis and inflammation. Our study may help to develop future lipid-based therapies for catecholamine-induced cardiac damage. MDPI 2021-11-24 /pmc/articles/PMC8657733/ /pubmed/34884498 http://dx.doi.org/10.3390/ijms222312695 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Betz, Iris Rosa
Qaiyumi, Sarah Julia
Goeritzer, Madeleine
Thiele, Arne
Brix, Sarah
Beyhoff, Niklas
Grune, Jana
Klopfleisch, Robert
Greulich, Franziska
Uhlenhaut, Nina Henriette
Kintscher, Ulrich
Foryst-Ludwig, Anna
Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation
title Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation
title_full Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation
title_fullStr Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation
title_full_unstemmed Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation
title_short Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation
title_sort cardioprotective effects of palmitoleic acid (c16:1n7) in a mouse model of catecholamine-induced cardiac damage are mediated by ppar activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657733/
https://www.ncbi.nlm.nih.gov/pubmed/34884498
http://dx.doi.org/10.3390/ijms222312695
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