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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
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. |
format | Online Article Text |
id | pubmed-7921966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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