Dataset Information

Macrophage-produced VEGFC is induced by efferocytosis to resolve inflammation and improve ventricular function after myocardial infarction (ChIP-Seq)

ABSTRACT: Recent reports have suggested a protective role for vascular endothelial growth factor C (VEGFC) during acute cardiac lymphangiogenesis post MI. Glinton et al. report that defective efferocytosis by macrophages after experimental MI leads to a reduction in cardiac lymphangiogenesis and Vegfc expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE196865 | GEO | 2022/03/31

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:To determine whether lymphangiogenesis is required for cardiac regeneration, vegfc(hy-/-);vegfd(-/-) double mutants and control hearts were collected and analyzed at 180 days after cryoinjury, this corresponds to a time point when the regenerative response is normally completed in wild-type zebrafish. Surprisingly, the vast majority (~70%) of vegfc(hy-/-);vegfd(-/-) mutants, which completely lack cardiac lymphatics, were able to mount a complete regenerative response without any signs of fibrosis. We found that the cardiac regenerative response was impaired only in a subset (3/8) of vegfc(hy-/-);vegfd(-/-) mutants, which were characterized by large deposits of fibrotic scar tissue present at the injury site. To profile vegfc/d-dependent genetic pathways contributing to lymphangiogenesis in cardiac regeneration, we performed RNA-seq on cryosections from control and mutant ventricles at 180 days following cryoinjury. Overall, vegfc(hy-/-);vegfd(-/-) mutant ventricles were characterized by an up-regulation of pathways related to metabolism, inflammation, hemostasis, negative regulation of FGFR signaling, translation, protein maturation and nonsense mediated decay compared to control hearts. These findings are consistent with the cardiac hypertrophy phenotype in vegfc(hy-/-);vegfd(-/-) mutants. To determine the molecular basis of the regenerative capacity within the mutant fish population, we next compared the transcriptional profiles of vegfc(hy-/-);vegfd(-/-) mutant hearts that did not regenerate (n=3) with the profiles of mutant hearts which recovered completely (n=5) at 180 days post cryoinjury. The subset of vegfc(hy-/-);vegfd(-/-) mutant hearts that failed to regenerate were characterized by an enrichment of inflammatory pathways, in particular TRAF6-mediated IRF7 activation, interferon alpha beta signaling and regulation of IFNA signaling. These findings suggest that loss of the vegfc/d signaling axis causes a sustained and pronounced inflammatory response following injury. This change in the cardiac micro-environment seems to favor adverse conditions which impair the regenerative process.

Dataset Information

Macrophage-produced VEGFC is induced by efferocytosis to resolve inflammation and improve ventricular function after myocardial infarction (ChIP-Seq)

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure