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Status |
Public on Sep 07, 2021 |
Title |
Development of Specific Therapy Against Right Ventricular Failure |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Right ventricular (RV) failure plays a critical role in any type of heart failure. However, there is no specific therapy developed for RV failure. To understand RV failure, we focused on the RV specific genes. Global gene expression analysis showed that alternative complement pathway-related genes including C3 and Cfd were significantly upregulated in right ventricle in murine heart. We generated the RV failure by right ventricle-specific pressure overload model mice, pulmonary artery constriction (PAC), which induces RV failure around 14 days. In C3 knockout (C3KO) mice, PAC-induced RV dysfunction and fibrosis were significantly attenuated. C3a is produced from C3 by C3 convertase complex including Cfd. Cfd knockout mice also attenuated PAC-induced RV failure. Moreover, C3a receptor (C3aR) antagonist dramatically improved PAC-induced RV dysfunction in wild type mice. Here we revealed the crucial role of C3-Cfd-C3a-C3aR axis in RV failure and highlight the potential therapeutic target for RV failure with no pharmacologic option.
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Overall design |
Murine hearts were separated into RV, LV and ventricular septum using different individuals for each experiment.
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Contributor(s) |
Ito S, Seki T, Yuasa S |
Citation(s) |
36109509 |
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Submission date |
Sep 06, 2021 |
Last update date |
Sep 27, 2022 |
Contact name |
Shogo Ito |
E-mail(s) |
itoshogo@keio.jp, itopap122@icloud.com
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Organization name |
Keio University School of Medicine
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Department |
Cardiology
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Lab |
Yuasa Lab.
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Street address |
35 Shinanomachi Shinjuku-ku
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City |
Tokyo |
ZIP/Postal code |
160-0016 |
Country |
Japan |
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Platforms (1) |
GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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Samples (10)
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Relations |
BioProject |
PRJNA761093 |