AAV9-mediated overexpression of the mechano-sensing gene Csrp3 at the border zone prevented adverse left ventricular remodeling after myocardial infarction in mice, whereas its knockdown aggravated cardiac dysfunction.
Mechano-sensing genes like Csrp3 at the border zone act as adaptive regulators to prevent left ventricular remodeling after myocardial infarction.
The 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.
Yamada et al. (Thu,) conducted a other in Myocardial Infarction. AAV9-mediated Csrp3 overexpression or shRNA knockdown vs. Control AAV9 was evaluated on Left ventricular remodeling and cardiac function (fractional shortening, LVDd, LVDs). AAV9-mediated overexpression of the mechano-sensing gene Csrp3 at the border zone prevented adverse left ventricular remodeling after myocardial infarction in mice, whereas its knockdown aggravated cardiac dysfunction.