NEAT1 Coordinates a PDLIM5-CACNA1C Regulatory Program Associated with a Potentially Arrhythmogenic Cardiomyocyte State in the Border Zone During Early Myocardial Infarction.

Patients with early-stage myocardial infarction (MI) are at high risk of malignant ventricular arrhythmias, yet the cell-type-specific molecular landscape associated with post-infarction arrhythmogenesis has not been systematically characterized. This study integrates single-nucleus and spatial transcriptomics to define a cardiomyocyte subpopulation in early MI and dissect the NEAT1-centered regulatory network driving its ion channel remodeling. Single-nucleus transcriptomic data from post-MI human hearts were re-analyzed to identify a distinct subpopulation, termed arrhythmia-potential cardiomyocytes (aCMs), within the infarct border zone, characterized by pronounced ion channel remodeling. Gene co-expression network analysis revealed two modules highly associated with aCMs, in which NEAT1 correlated with the calcium channel gene CACNA1C and the LIM domain protein PDLIM5. All three genes were upregulated in hypoxic rat cardiomyocytes; siRNA-mediated knockdown confirmed that NEAT1 silencing downregulated CACNA1C and PDLIM5 expression, consistent with in silico knockout predictions. A ceRNA network further identified hsa-miR-204-5p/211-5p as a key mediator consistent with regulatory axis. These findings suggest that cardiomyocytes in the early MI border zone exhibit ion channel remodeling driven by elevated NEAT1, which may modulate CACNA1C and PDLIM5 through a microRNA-mediated ceRNA network, suggesting that targeting NEAT1 may warrant further investigation for preventing malignant arrhythmias in early-stage MI.