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METTL14 inhibits atherogenesis by epigenetically activating PPAR-α/γ transcription and fatty acid oxidation in VSMCs - PubMed

6 hours ago
  • #Atherosclerosis
  • #Epigenetics
  • #Lipid Metabolism
  • METTL14 inhibits atherogenesis by activating PPAR-α/γ transcription and fatty acid oxidation in VSMCs.
  • VSMC-specific Mettl14 knockout mice showed accelerated foam cell formation and exacerbated atherosclerosis.
  • METTL14 regulates phenotypic switching of VSMCs and modulates VSMC-derived macrophage-like cells in plaques.
  • METTL14 enhances SETD1A-mediated H3K4 trimethylation to regulate Ppara and Pparg transcription in an m6A-independent manner.
  • Activation of PPAR-γ with rosiglitazone restored mitochondrial OXPHOS in Mettl14-deficient VSMCs, reducing lipid accumulation.
  • AAV gene therapy recapitulating Mettl14 expression inhibited atherosclerosis progression without liver dysfunction.