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Female-Biased VSMC GRNs Predict MYH9 as Regulator of Fibrous Plaque Phenotype - PubMed

4 hours ago
  • #Sex Differences
  • #Atherosclerosis
  • #Gene Regulatory Networks
  • Atherosclerosis involves unstable atheromatous and stable fibrous plaques, with fibrous plaques in females under 50 being less understood.
  • Sex-specific gene regulatory networks (GRNs) from human vascular smooth muscle cells revealed two female-biased networks: GRNfloralwhite (inflammatory pathways) and GRNyellowgreen (actin remodeling pathways).
  • Single-cell RNA-sequencing confirmed sex-specific network activity in plaque cells, with GRNyellowgreen enriched for contractile and vascular development pathways.
  • Bayesian network modeling identified MYH9 (myosin heavy chain 9) as a key driver gene, with elevated MYH9 linked to increased smooth muscle cell content and reduced lipid in female plaques.
  • Proteomic analyses validated MYH9 upregulation in female fibrous plaques, associating it with stable plaque characteristics, highlighting sex-specific regulation in atherosclerosis.