Abstract 2121: SUV39H1 Mediated Regulation Of KLF4 And KDM4a Coordinate Smooth Muscle Cell Phenotypic Plasticity

• DOI: 10.1161/atvb.44.suppl_1.2121
• Publication Date: 2024-07-24T13:03:55Z
• Authors: Payel Chatterjee; Raja Chakraborty; Ashley Sizer; Yi Xie; John Hwa; Kathleen A Martin
• Keywords: KLF4

Background: The phenotypic plasticity of vascular smooth muscle cells is central to growth and remodeling processes, but also underlies many cardiovascular pathologies, including atherosclerosis, restenosis, intimal hyperplasia. This ability VSMCs reversibly differentiate dedifferentiate incompletely understood. SUV39H1, a histone methyltransferase, that generates the H3K9Me3 mark results in epigenetic transcriptional repression. We hypothesized SUV39H1 plays key role VSMC plasticity. Methods: applied knockdown, qPCR, western blotting, chromatin immunoprecipitation (ChIP) assays, RNA-Seq, murine injury determine Results: A qPCR array screen regulators revealed upregulated with PDGF-induced dedifferentiation downregulated rapamycin-induced differentiation hCASMCs. Knockdown induces differentiation-specific hCASMC contractile genes functional contractility while decreased migration, proliferation, de-differentiation-associated gene expression. RNA-seq transcriptomics confirmed changes multiple pathways consistent for promoting dedifferentiation. Mechanistically, knockdown suppressed expression KLF4, master factor, decreasing KLF4 mRNA stability upregulating miRNA143. increased KDM4a, an enzyme removes H3K9me3 marks. In vivo, we noted significant increase carotid artery ligation-induced hyperplasia compared uninjured vessels. Conclusion: identify as regulator phenotype whose activity vitro vivo . PDGF promotes repressive marks at by (writer), which inhibits KDM4a (eraser) regulates Understanding may reveal new therapeutic strategies treating diseases.