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The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta

Background: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown. Methods: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed b...

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Autores principales: Perera-Gonzalez, Mireia, Kiss, Attila, Kaiser, Philipp, Holzweber, Michael, Nagel, Felix, Watzinger, Simon, Acar, Eylem, Szabo, Petra Lujza, Gonçalves, Inês Fonseca, Weber, Lukas, Pilz, Patrick Michael, Budinsky, Lubos, Helbich, Thomas, Podesser, Bruno Karl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921966/
https://www.ncbi.nlm.nih.gov/pubmed/33670747
http://dx.doi.org/10.3390/ijms22042023
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author Perera-Gonzalez, Mireia
Kiss, Attila
Kaiser, Philipp
Holzweber, Michael
Nagel, Felix
Watzinger, Simon
Acar, Eylem
Szabo, Petra Lujza
Gonçalves, Inês Fonseca
Weber, Lukas
Pilz, Patrick Michael
Budinsky, Lubos
Helbich, Thomas
Podesser, Bruno Karl
author_facet Perera-Gonzalez, Mireia
Kiss, Attila
Kaiser, Philipp
Holzweber, Michael
Nagel, Felix
Watzinger, Simon
Acar, Eylem
Szabo, Petra Lujza
Gonçalves, Inês Fonseca
Weber, Lukas
Pilz, Patrick Michael
Budinsky, Lubos
Helbich, Thomas
Podesser, Bruno Karl
author_sort Perera-Gonzalez, Mireia
collection PubMed
description Background: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown. Methods: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed by debanding for 2 weeks in wild type (Wt) and TN-C knockout (TN-C KO) mice. Cardiac function was assessed by serial magnetic resonance imaging. The expression of fibrotic markers and drivers (angiotensin-converting enzyme-1, ACE-1) was determined in LV tissue as well as human cardiac fibroblasts (HCFs) after TN-C treatment. Results: Chronic pressure overload resulted in a significant decline in cardiac function associated with LV dilation as well as upregulation of TN-C, collagen 1 (Col 1), and ACE-1 in Wt as compared to TN-C KO mice. Reverse remodeling in Wt mice partially improved cardiac function and fibrotic marker expression; however, TN-C protein expression remained unchanged. In HCF, TN-C strongly induced the upregulation of ACE 1 and Col 1. Conclusions: Pressure overload, when lasting long enough to induce HF, has less potential for reverse remodeling in mice. This may be due to significant upregulation of TN-C expression, which stimulates ACE 1, Col 1, and alpha-smooth muscle actin (α-SMA) upregulation in fibroblasts. Consequently, addressing TN-C in LV hypertrophy might open a new window for future therapeutics.
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spelling pubmed-79219662021-03-03 The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta Perera-Gonzalez, Mireia Kiss, Attila Kaiser, Philipp Holzweber, Michael Nagel, Felix Watzinger, Simon Acar, Eylem Szabo, Petra Lujza Gonçalves, Inês Fonseca Weber, Lukas Pilz, Patrick Michael Budinsky, Lubos Helbich, Thomas Podesser, Bruno Karl Int J Mol Sci Article Background: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown. Methods: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed by debanding for 2 weeks in wild type (Wt) and TN-C knockout (TN-C KO) mice. Cardiac function was assessed by serial magnetic resonance imaging. The expression of fibrotic markers and drivers (angiotensin-converting enzyme-1, ACE-1) was determined in LV tissue as well as human cardiac fibroblasts (HCFs) after TN-C treatment. Results: Chronic pressure overload resulted in a significant decline in cardiac function associated with LV dilation as well as upregulation of TN-C, collagen 1 (Col 1), and ACE-1 in Wt as compared to TN-C KO mice. Reverse remodeling in Wt mice partially improved cardiac function and fibrotic marker expression; however, TN-C protein expression remained unchanged. In HCF, TN-C strongly induced the upregulation of ACE 1 and Col 1. Conclusions: Pressure overload, when lasting long enough to induce HF, has less potential for reverse remodeling in mice. This may be due to significant upregulation of TN-C expression, which stimulates ACE 1, Col 1, and alpha-smooth muscle actin (α-SMA) upregulation in fibroblasts. Consequently, addressing TN-C in LV hypertrophy might open a new window for future therapeutics. MDPI 2021-02-18 /pmc/articles/PMC7921966/ /pubmed/33670747 http://dx.doi.org/10.3390/ijms22042023 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Perera-Gonzalez, Mireia
Kiss, Attila
Kaiser, Philipp
Holzweber, Michael
Nagel, Felix
Watzinger, Simon
Acar, Eylem
Szabo, Petra Lujza
Gonçalves, Inês Fonseca
Weber, Lukas
Pilz, Patrick Michael
Budinsky, Lubos
Helbich, Thomas
Podesser, Bruno Karl
The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta
title The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta
title_full The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta
title_fullStr The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta
title_full_unstemmed The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta
title_short The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta
title_sort role of tenascin c in cardiac reverse remodeling following banding–debanding of the ascending aorta
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921966/
https://www.ncbi.nlm.nih.gov/pubmed/33670747
http://dx.doi.org/10.3390/ijms22042023
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