Cardiac Fibroblasts Play Pathogenic Roles in Idiopathic Restrictive Cardiomyopathy
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- Tsuru Hirofumi
- Department of Pediatrics, Osaka University Graduate School of Medicine
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- Ishida Hidekazu
- Department of Pediatrics, Osaka University Graduate School of Medicine
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- Narita Jun
- Department of Pediatrics, Osaka University Graduate School of Medicine
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- Ishii Ryo
- Department of Pediatrics, Osaka University Graduate School of Medicine
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- Suginobe Hidehiro
- Department of Pediatrics, Osaka University Graduate School of Medicine
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- Ishii Yoichiro
- Department of Pediatric Cardiology, Osaka Women’s and Children’s Hospital
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- Wang Renjie
- Department of Pediatrics, Osaka University Graduate School of Medicine
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- Kogaki Shigetoyo
- Department of Pediatrics, Osaka University Graduate School of Medicine Department of Pediatrics and Neonatology, Osaka General Medical Center
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- Taira Masaki
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine
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- Ueno Takayoshi
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine
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- Miyashita Yohei
- Department of Cardiology, Osaka University Graduate School of Medicine
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- Kioka Hidetaka
- Department of Cardiology, Osaka University Graduate School of Medicine
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- Asano Yoshihiro
- Department of Cardiology, Osaka University Graduate School of Medicine
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- Sawa Yoshiki
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine
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- Ozono Keiichi
- Department of Pediatrics, Osaka University Graduate School of Medicine
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説明
<p>Background:Restrictive cardiomyopathy (RCM) is characterized by impaired ventricular relaxation. Although several mutations were reported in some patients, no mutations were identified in cardiomyocyte expressing genes of other patients, indicating that pathological mechanisms underlying RCM could not be determined by cardiomyocytes only. Cardiac fibroblasts (CFs) are a major cell population in the heart; however, the pathological roles of CFs in cardiomyopathy are not fully understood.</p><p>Methods and Results:This study established 4 primary culture lines of CFs from RCM patients and analyzed their cellular physiology, the effects on the contraction and relaxation ability of healthy cardiomyocytes under co-culture with CFs, and RNA sequencing. Three of four patients hadTNNI3mutations. There were no significant alterations in cell proliferation, apoptosis, migration, activation, and attachment. However, when CFs from RCM patients were co-cultured with healthy cardiomyocytes, the relaxation velocity of cardiomyocytes was significantly impaired both under direct and indirect co-culture conditions. RNA sequencing revealed that gene expression profiles of CFs in RCM were clearly distinct from healthy CFs. The differential expression gene analysis identified that several extracellular matrix components and cytokine expressions were dysregulated in CFs from RCM patients.</p><p>Conclusions:The comprehensive gene expression patterns were altered in RCM-derived CFs, which deteriorated the relaxation ability of cardiomyocytes. The specific changes in extracellular matrix composition and cytokine secretion from CFs might affect pathological behavior of cardiomyocytes in RCM.</p>
収録刊行物
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- Circulation Journal
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Circulation Journal 85 (5), 677-686, 2021-04-23
一般社団法人 日本循環器学会
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詳細情報 詳細情報について
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- CRID
- 1390569258152994944
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- NII論文ID
- 130008028981
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- NII書誌ID
- AA11591968
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- ISSN
- 13474820
- 13469843
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- NDL書誌ID
- 031419711
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- PubMed
- 33583869
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
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