Scientists Find Key Switch That Blocks Artery-Clogging Cell Transformation
Researchers identified a protein called BHLHE40 that controls whether cells in artery walls develop into dangerous foam cells that fuel atherosclerosis. The discovery could unlock new drug targets for preventing heart disease, the leading cause of death globally and a major cost driver for healthcare systems and insurers.
Originaltitel: Atherosclerosis Profiling Reveals BHLHE40 as a Candidate Modulator of VSMC
BACKGROUND: Vascular smooth muscle cells (VSMCs) play a central role in atherosclerosis by undergoing phenotypic modulation from a quiescent, contractile state to a range of synthetic phenotypes, including fibroblast-like, macrophage-like, and lipid-laden foam cell-like states. However, a comprehensive multimodal characterization and understanding of the transcriptional programs driving these transitions remain incomplete. METHODS: To comprehensively define the phenotypic diversity of VSMCs during atherosclerosis progression, we performed in-depth profiling using cellular indexing of transcriptomes and epitopes by sequencing and bulk RNA sequencing in a VSMC-lineage-tracing atherosclerotic mouse model. Insights from these data sets guided the design of targeted in vitro experiments to investigate candidate regulatory mechanisms. RESULTS: reprogrammed immune, cell cycle, and lipid homeostasis genes in cultured VSMC and suppressed VSMC phenotypic switching and foam cell characteristics, consistent with a potential regulatory role in VSMC modulation. CONCLUSIONS: These findings advance our understanding of VSMC phenotypic modulation in atherosclerosis and implicate BHLHE40 as a candidate transcriptional regulator of this process. Elucidating mechanisms governing VSMC plasticity may offer new therapeutic opportunities to reduce cardiovascular risk by targeting disease-driving cellular transitions.