Experimental MI induces region-specific transcriptional remodeling in microglia, reducing translation and proteostasis pathways with altered mitochondrial mass.
Does experimental myocardial infarction induce transcriptional remodeling and altered metabolic regulation in central nervous system microglia in mice?
Experimental myocardial infarction induces early, region-specific transcriptional downregulation of energy-intensive and proteostasis-related pathways in brain microglia, highlighting a systemic heart-brain axis response to cardiac injury.
Beyond cardiac impairment, myocardial infarction (MI) affects the central nervous system (CNS), where it has been associated with neuroinflammation and cognitive dysfunction. Microglia, the resident immune cells of the CNS, are key regulators of neuroinflammatory processes. However, the transcriptional landscape of microglia following MI remains incompletely understood. We hypothesized that MI induces transcriptional remodeling in microglia that may reflect altered metabolic regulation. Male C57BL/6J mice underwent permanent LAD ligation or sham surgery. Five days post-MI, CD45-intermediate and SiglecH/CD11b-positive immune cells were isolated from cortical and subcortical regions by FACS and subjected to single-cell RNA sequencing. Complementary exploratory metabolic assays included assessment of mitochondrial mass and membrane potential as well as glucose uptake. Microglia represented the predominant immune cell population in both the cortex and subcortex. Subclustering revealed a significantly increased proportion of a “low translational” microglial subset after MI. Pseudobulk differential expression and gene set enrichment analyses demonstrated significant downregulation of translation-related pathways in cortical microglia and proteostasis-associated pathways in subcortical microglia. These transcriptional changes were accompanied by a significant reduction in mitochondrial mass and metabolic observations consistent with altered energetic regulation, although several functional readouts did not reach statistical significance. Experimental MI is associated with region-specific transcriptional remodeling of microglia, characterized by reduced expression of energy-intensive and proteostasis-related pathways. Exploratory metabolic observations are consistent with altered energetic regulation but require confirmation in adequately powered studies. These findings suggest that systemic cardiac injury is linked to microglial transcriptional adaptation in the early post-infarction phase.
Traub et al. (2026) studied this question. Experimental MI induces region-specific transcriptional remodeling in microglia, reducing translation and proteostasis pathways with altered mitochondrial mass.