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Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS
Cancer and heart diseases are the two leading causes of mortality and morbidity worldwide. Many cancer patients undergo heart-related complications resulting in high incidences of mortality. It is generally hypothesized that cardiac dysfunction in cancer patients occurs due to cardiotoxicity induced...
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/PMC8389295/ https://www.ncbi.nlm.nih.gov/pubmed/34439547 http://dx.doi.org/10.3390/antiox10081299 |
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author | Karekar, Priyanka Jensen, Haley N. Russart, Kathryn L. G. Ponnalagu, Devasena Seeley, Sarah Sanghvi, Shridhar Smith, Sakima A. Pyter, Leah M. Singh, Harpreet Gururaja Rao, Shubha |
author_facet | Karekar, Priyanka Jensen, Haley N. Russart, Kathryn L. G. Ponnalagu, Devasena Seeley, Sarah Sanghvi, Shridhar Smith, Sakima A. Pyter, Leah M. Singh, Harpreet Gururaja Rao, Shubha |
author_sort | Karekar, Priyanka |
collection | PubMed |
description | Cancer and heart diseases are the two leading causes of mortality and morbidity worldwide. Many cancer patients undergo heart-related complications resulting in high incidences of mortality. It is generally hypothesized that cardiac dysfunction in cancer patients occurs due to cardiotoxicity induced by therapeutic agents, used to treat cancers and/or cancer-induced cachexia. However, it is not known if localized tumors or unregulated cell growth systemically affect heart function before treatment, and/or prior to the onset of cachexia, hence, making the heart vulnerable to structural or functional abnormalities in later stages of the disease. We incorporated complementary mouse and Drosophila models to establish if tumor induction indeed causes cardiac defects even before intervention with chemotherapy or onset of cachexia. We focused on one of the key pathways involved in irregular cell growth, the Hippo–Yorkie (Yki), pathway. We used overexpression of the transcriptional co-activator of the Yki signaling pathway to induce cellular overgrowth, and show that Yki overexpression in the eye tissue of Drosophila results in compromised cardiac function. We rescue these cardiac phenotypes using antioxidant treatment, with which we conclude that the Yki induced tumorigenesis causes a systemic increase in ROS affecting cardiac function. Our results show that systemic cardiac dysfunction occurs due to abnormal cellular overgrowth or cancer elsewhere in the body; identification of specific cardiac defects associated with oncogenic pathways can facilitate the possible early diagnosis of cardiac dysfunction. |
format | Online Article Text |
id | pubmed-8389295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83892952021-08-27 Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS Karekar, Priyanka Jensen, Haley N. Russart, Kathryn L. G. Ponnalagu, Devasena Seeley, Sarah Sanghvi, Shridhar Smith, Sakima A. Pyter, Leah M. Singh, Harpreet Gururaja Rao, Shubha Antioxidants (Basel) Article Cancer and heart diseases are the two leading causes of mortality and morbidity worldwide. Many cancer patients undergo heart-related complications resulting in high incidences of mortality. It is generally hypothesized that cardiac dysfunction in cancer patients occurs due to cardiotoxicity induced by therapeutic agents, used to treat cancers and/or cancer-induced cachexia. However, it is not known if localized tumors or unregulated cell growth systemically affect heart function before treatment, and/or prior to the onset of cachexia, hence, making the heart vulnerable to structural or functional abnormalities in later stages of the disease. We incorporated complementary mouse and Drosophila models to establish if tumor induction indeed causes cardiac defects even before intervention with chemotherapy or onset of cachexia. We focused on one of the key pathways involved in irregular cell growth, the Hippo–Yorkie (Yki), pathway. We used overexpression of the transcriptional co-activator of the Yki signaling pathway to induce cellular overgrowth, and show that Yki overexpression in the eye tissue of Drosophila results in compromised cardiac function. We rescue these cardiac phenotypes using antioxidant treatment, with which we conclude that the Yki induced tumorigenesis causes a systemic increase in ROS affecting cardiac function. Our results show that systemic cardiac dysfunction occurs due to abnormal cellular overgrowth or cancer elsewhere in the body; identification of specific cardiac defects associated with oncogenic pathways can facilitate the possible early diagnosis of cardiac dysfunction. MDPI 2021-08-18 /pmc/articles/PMC8389295/ /pubmed/34439547 http://dx.doi.org/10.3390/antiox10081299 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 Karekar, Priyanka Jensen, Haley N. Russart, Kathryn L. G. Ponnalagu, Devasena Seeley, Sarah Sanghvi, Shridhar Smith, Sakima A. Pyter, Leah M. Singh, Harpreet Gururaja Rao, Shubha Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS |
title | Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS |
title_full | Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS |
title_fullStr | Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS |
title_full_unstemmed | Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS |
title_short | Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS |
title_sort | tumor-induced cardiac dysfunction: a potential role of ros |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389295/ https://www.ncbi.nlm.nih.gov/pubmed/34439547 http://dx.doi.org/10.3390/antiox10081299 |
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