著者
Hirofumi Tsuru Hidekazu Ishida Jun Narita Ryo Ishii Hidehiro Suginobe Yoichiro Ishii Renjie Wang Shigetoyo Kogaki Masaki Taira Takayoshi Ueno Yohei Miyashita Hidetaka Kioka Yoshihiro Asano Yoshiki Sawa Keiichi Ozono
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.85, no.5, pp.677-686, 2021-04-23 (Released:2021-04-23)
参考文献数
38
被引用文献数
8

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.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.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.

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当科医師の大阪大学での研究で #拘束型心筋症 患者由来の線維芽細胞を正常心筋細胞と培養すると、拡張が阻害されることが分かりました。心筋症の病態がわかり治療できるようになることを祈っています。 #健康ハートの日 ❤️ #健康ハートウィーク2022
最近では大阪大学で基礎研究を行った例があります。心臓線維芽細胞を使用した基礎研究で、線維芽細胞が心臓の拡張に影響し、#拘束型心筋症 の原因となっているかもしれない、との結果をまとめました。 #小児循環研究室 #RCM https://t.co/zrcYDl8iqI
When cardiac fibroblasts from restrictive cardiomyopathy patients were co-cultured with healthy cardiomyocytes, the relaxation velocity was impaired. Fibroblasts might affect pathological behavior of cardiomyocytes. #TNNI3 #RCM #小児循環研究室 @JCIRC_IPR https://t.co/zrcYDkQ9cA
#新潟大学小児科循環器班 の水流先生が阪大に国内留学されていた際に研究していたものがCirculation Journalに掲載されました! 論文掲載おめでとうございます! Cardiac Fibroblasts Play Pathogenic Roles in Idiopathic Restrictive Cardiomyopathy https://t.co/n4a759Kans #日本循環器学会 https://t.co/7WqGHHsYpN

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