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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Information Science and Technology / Faculty of Information Science and Technology >
Peer-reviewed Journal Articles, etc >
Atomic force microscopy identifies the alteration of rheological properties of the cardiac fibroblasts in idiopathic restrictive cardiomyopathy
| Title: | Atomic force microscopy identifies the alteration of rheological properties of the cardiac fibroblasts in idiopathic restrictive cardiomyopathy |
| Authors: | Matsumoto, Mizuki Browse this author | | Tsuru, Hirofumi Browse this author | | Suginobe, Hidehiro Browse this author →KAKEN DB | | Narita, Jun Browse this author →KAKEN DB | | Ishii, Ryo Browse this author →KAKEN DB | | Hirose, Masaki Browse this author | | Hashimoto, Kazuhisa Browse this author | | Wang, Renjie Browse this author | | Yoshihara, Chika Browse this author | | Ueyama, Atsuko Browse this author | | Tanaka, Ryosuke Browse this author | | Ozono, Keiichi Browse this author →KAKEN DB | | Okajima, Takaharu Browse this author →KAKEN DB | | Ishida, Hidekazu Browse this author →KAKEN DB |
| Issue Date: | 29-Sep-2022 |
| Publisher: | PLOS |
| Journal Title: | PLoS ONE |
| Volume: | 17 |
| Issue: | 9 |
| Start Page: | e0275296 |
| Publisher DOI: | 10.1371/journal.pone.0275296 |
| Abstract: | Restrictive cardiomyopathy (RCM) is a rare disease characterized by increased ventricular stiffness and preserved ventricular contraction. Various sarcomere gene variants are known to cause RCM; however, more than a half of patients do not harbor such pathogenic variants. We recently demonstrated that cardiac fibroblasts (CFs) play important roles in inhibiting the diastolic function of cardiomyocytes via humoral factors and direct cell-cell contact regardless of sarcomere gene mutations. However, the mechanical properties of CFs that are crucial for intercellular communication and the cardiomyocyte microenvironment remain less understood. In this study, we evaluated the rheological properties of CFs derived from pediatric patients with RCM and healthy control CFs via atomic force microscopy. Then, we estimated the cellular modulus scale factor related to the cell stiffness, fluidity, and Newtonian viscosity of single cells based on the single power-law rheology model and analyzed the comprehensive gene expression profiles via RNA-sequencing. RCM-derived CFs showed significantly higher stiffness and viscosity and lower fluidity compared to healthy control CFs. Furthermore, RNA-sequencing revealed that the signaling pathways associated with cytoskeleton elements were affected in RCM CFs; specifically, cytoskeletal actin-associated genes (ACTN1, ACTA2, and PALLD) were highly expressed in RCM CFs, whereas several tubulin genes (TUBB3, TUBB, TUBA1C, and TUBA1B) were down-regulated. These results implies that the signaling pathways associated with cytoskeletal elements alter the rheological properties of RCM CFs, particularly those related to CF-cardiomyocyte interactions, thereby leading to diastolic cardiac dysfunction in RCM. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/88103 |
| Appears in Collections: | 情報科学院・情報科学研究院 (Graduate School of Information Science and Technology / Faculty of Information Science and Technology) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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