Abstract
AbstractThe underlying mechanisms of ventricular remodeling after myocardial infarction (MI) remain largely unknown. In this study, we performed an integrative analysis of spatial transcriptomics and single-nucleus RNA sequencing (snRNA-seq) in a murine MI model and found that mechanical stress-response genes are expressed at the border zone and play a critical role in left ventricular remodeling after MI. An integrative analysis of snRNA-seq and spatial transcriptome of the heart tissue after MI identified the unique cluster that appeared at the border zone in an early stage, highly expressing mechano-sensing genes, such as Csrp3. AAV9-mediated gene silencing and overexpression of Csrp3 demonstrated that upregulation of Csrp3 plays critical roles in preventing cardiac remodeling after MI by regulation of genes associated with mechano-sensing. Overall, our study not only provides an insight into spatiotemporal molecular changes after MI but also highlights that the mechano-sensing genes at the border zone act as adaptive regulators of left ventricular remodeling.
Funder
Japan Foundation for Applied Enzymology
Grants-in-Aid for Young Scientists SENSHIN Medical Research Foundation MSD Life Science Foundation
SENSHIN Medical Research Foundation
Kanae Foundation for the Promotion of Medical Science
Astellas Foundation for Research on Metabolic Disorders
NOVARTIS Foundation (Japan) for the Promotion of Science (NOVARTIS Foundation
Japanese Circulation Society
Takeda Science Foundation
Cell Science Research Foundation
Japan Agency for Medical Research and Development
MSD Life Science Foundation Tokyo Biomedical Research Foundation
Grand-in-Aid for Young Scientists
Publisher
Springer Science and Business Media LLC
Cited by
17 articles.
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