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SMOC2 accelerates myocardial fibrosis following myocardial infarction by promoting lipid peroxidation through inhibition of the LKB1/AMPKα/FOXO3 pathway - PubMed

7 hours ago
  • #Lipid Peroxidation
  • #Myocardial Infarction
  • #Fibrosis
  • SMOC2, an extracellular matrix-associated protein, is significantly upregulated after myocardial infarction (MI) and in cardiac fibroblasts under hypoxia/reoxygenation (H/R) stress.
  • Fibroblast-specific SMOC2 overexpression worsens myocardial injury, inflammation, and fibrosis, while SMOC2 knockout alleviates these effects and improves cardiac function.
  • SMOC2 interacts with integrin αvβ5 to inhibit the LKB1/AMPKα/FOXO3 signaling pathway, leading to reduced antioxidant defense, increased lipid peroxidation, and elevated oxidative stress.
  • RNA sequencing and metabolomic analyses show that SMOC2 disrupts lipid metabolism during cardiac remodeling.
  • Targeting SMOC2 or reactivating the AMPKα/FOXO3 axis may be a potential therapeutic strategy to mitigate adverse cardiac remodeling post-MI.