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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...

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Autores principales: Kusakari, Yoichiro, Urashima, Takashi, Shimura, Daisuke, Amemiya, Erika, Miyasaka, Genki, Yokota, Shunsuke, Fujimoto, Yoshitaka, Akaike, Toru, Inoue, Takahiro, Minamisawa, Susumu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
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.
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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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