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Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding
Interstitial myocardial fibrosis is one of the factors responsible for dysfunction of the heart. However, how interstitial fibrosis affects cardiac function and excitation-contraction coupling (E-C coupling) has not yet been clarified. We developed an animal model of right ventricular (RV) hypertrop...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222608/ https://www.ncbi.nlm.nih.gov/pubmed/28068381 http://dx.doi.org/10.1371/journal.pone.0169564 |
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author | Kusakari, Yoichiro Urashima, Takashi Shimura, Daisuke Amemiya, Erika Miyasaka, Genki Yokota, Shunsuke Fujimoto, Yoshitaka Akaike, Toru Inoue, Takahiro Minamisawa, Susumu |
author_facet | Kusakari, Yoichiro Urashima, Takashi Shimura, Daisuke Amemiya, Erika Miyasaka, Genki Yokota, Shunsuke Fujimoto, Yoshitaka Akaike, Toru Inoue, Takahiro Minamisawa, Susumu |
author_sort | Kusakari, Yoichiro |
collection | PubMed |
description | Interstitial myocardial fibrosis is one of the factors responsible for dysfunction of the heart. However, how interstitial fibrosis affects cardiac function and excitation-contraction coupling (E-C coupling) has not yet been clarified. We developed an animal model of right ventricular (RV) hypertrophy with fibrosis by pulmonary artery (PA) banding in rats. Two, four, and six weeks after the PA-banding operation, the tension and intracellular Ca(2+) concentration of RV papillary muscles were simultaneously measured (n = 33). The PA-banding rats were clearly divided into two groups by the presence or absence of apparent interstitial fibrosis in the papillary muscles: F+ or F- group, respectively. The papillary muscle diameter and size of myocytes were almost identical between F+ and F-, although the RV free wall weight was heavier in F+ than in F-. F+ papillary muscles exhibited higher stiffness, lower active tension, and lower Ca(2+) responsiveness compared with Sham and F- papillary muscles. In addition, we found that the time to peak Ca(2+) had the highest correlation coefficient to percent of fibrosis among other parameters, such as RV weight and active tension of papillary muscles. The phosphorylation level of troponin I in F+ was significantly higher than that in Sham and F-, which supports the idea of lower Ca(2+) responsiveness in F+. We also found that connexin 43 in F+ was sparse and disorganized in the intercalated disk area where interstitial fibrosis strongly developed. In the present study, the RV papillary muscles obtained from the PA-banding rats enabled us to directly investigate the relationship between fibrosis and cardiac dysfunction, the impairment of E-C coupling in particular. Our results suggest that interstitial fibrosis worsens cardiac function due to 1) the decrease in Ca(2+) responsiveness and 2) the asynchronous activation of each cardiac myocyte in the fibrotic preparation due to sparse cell-to-cell communication. |
format | Online Article Text |
id | pubmed-5222608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52226082017-01-19 Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding Kusakari, Yoichiro Urashima, Takashi Shimura, Daisuke Amemiya, Erika Miyasaka, Genki Yokota, Shunsuke Fujimoto, Yoshitaka Akaike, Toru Inoue, Takahiro Minamisawa, Susumu PLoS One Research Article Interstitial myocardial fibrosis is one of the factors responsible for dysfunction of the heart. However, how interstitial fibrosis affects cardiac function and excitation-contraction coupling (E-C coupling) has not yet been clarified. We developed an animal model of right ventricular (RV) hypertrophy with fibrosis by pulmonary artery (PA) banding in rats. Two, four, and six weeks after the PA-banding operation, the tension and intracellular Ca(2+) concentration of RV papillary muscles were simultaneously measured (n = 33). The PA-banding rats were clearly divided into two groups by the presence or absence of apparent interstitial fibrosis in the papillary muscles: F+ or F- group, respectively. The papillary muscle diameter and size of myocytes were almost identical between F+ and F-, although the RV free wall weight was heavier in F+ than in F-. F+ papillary muscles exhibited higher stiffness, lower active tension, and lower Ca(2+) responsiveness compared with Sham and F- papillary muscles. In addition, we found that the time to peak Ca(2+) had the highest correlation coefficient to percent of fibrosis among other parameters, such as RV weight and active tension of papillary muscles. The phosphorylation level of troponin I in F+ was significantly higher than that in Sham and F-, which supports the idea of lower Ca(2+) responsiveness in F+. We also found that connexin 43 in F+ was sparse and disorganized in the intercalated disk area where interstitial fibrosis strongly developed. In the present study, the RV papillary muscles obtained from the PA-banding rats enabled us to directly investigate the relationship between fibrosis and cardiac dysfunction, the impairment of E-C coupling in particular. Our results suggest that interstitial fibrosis worsens cardiac function due to 1) the decrease in Ca(2+) responsiveness and 2) the asynchronous activation of each cardiac myocyte in the fibrotic preparation due to sparse cell-to-cell communication. Public Library of Science 2017-01-09 /pmc/articles/PMC5222608/ /pubmed/28068381 http://dx.doi.org/10.1371/journal.pone.0169564 Text en © 2017 Kusakari et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kusakari, Yoichiro Urashima, Takashi Shimura, Daisuke Amemiya, Erika Miyasaka, Genki Yokota, Shunsuke Fujimoto, Yoshitaka Akaike, Toru Inoue, Takahiro Minamisawa, Susumu Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding |
title | Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding |
title_full | Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding |
title_fullStr | Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding |
title_full_unstemmed | Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding |
title_short | Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding |
title_sort | impairment of excitation-contraction coupling in right ventricular hypertrophied muscle with fibrosis induced by pulmonary artery banding |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222608/ https://www.ncbi.nlm.nih.gov/pubmed/28068381 http://dx.doi.org/10.1371/journal.pone.0169564 |
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