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SAHH Deficiency Decreases Stability of Atherosclerotic Plaque and Induces VSMC Phenotype Switching via Epigenetic Upregulation of KLF4 and OCT4 - PubMed

3 days ago
  • #Epigenetic Regulation
  • #SAHH Deficiency
  • #Atherosclerosis
  • SAHH deficiency reduces atherosclerotic plaque stability and triggers VSMC phenotype switching.
  • The mechanism involves epigenetic upregulation of KLF4 and OCT4 through SAH accumulation.
  • SAHH deletion inhibits DNMT3b, leading to KLF4 promoter hypomethylation and increased expression.
  • OCT4 reactivation occurs via KLF4-dependent TET1-mediated promoter hydroxymethylation.
  • AMPK inhibition by SAHH deficiency downregulates TET2-mediated KLF4 promoter hydroxymethylation.
  • Lower SAHH activity and higher SAH levels correlate with unstable plaques in patients with cardiovascular disease.