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<p>Real or simulated microgravity induces a senescence-like modification of carotid artery in both human and animal observations, with the mechanisms not fully elucidated. Here, we aim to elucidate the role of sterol regulatory element-binding protein 1 (SREBP1, encoded by <i>Srebf1</i>) mediated lipogenesis in the process. Pharmacological activation of SREBP1 directly triggers senescence-like transformation in vascular smooth muscle cells (VSMC), while silencing <i>Srebf1</i> exerts an opposite effect. Mechanistically, SREBP1-mediated lipogenesis upregulates acetyl-CoA pool to increase histone acetylation, modifying the chromatin accessibility which limiting recruitment of SRF/myocardin complexes to CArG boxes of contractile genes and opening the chromatin accessibility of aging genes. <i>Srebf1</i> knockdown and local delivery of lentivirus or AAV-mediated VSMC specific expressing sh-<i>Srebf1</i> significantly attenuates the senescence-like transformation of VSMC both in vitro and in vivo. Our findings reveal a previously unrecognized feature of SREBP1-mediated lipogenesis in vascular biology and SM-induced carotid artery remodeling.</p>

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SREBP1-mediated lipogenesis promotes dedifferentiation and senescence of vascular smooth muscle cells through epigenetic remodeling

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月26日

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  • Bowen Li,
  • Kaixiang Zhou,
  • Anan Yin,
  • Yonghong Liu,
  • Xichen Wang,
  • Yujia Cui,
  • Fangfang Liu,
  • Qiurong Liu,
  • Hongjing Zheng,
  • Zhiqiang Mu,
  • Kun Chen,
  • Yuanming Wu,
  • Yaoming Chang,
  • Junxiang Bao

摘要

Real or simulated microgravity induces a senescence-like modification of carotid artery in both human and animal observations, with the mechanisms not fully elucidated. Here, we aim to elucidate the role of sterol regulatory element-binding protein 1 (SREBP1, encoded by Srebf1) mediated lipogenesis in the process. Pharmacological activation of SREBP1 directly triggers senescence-like transformation in vascular smooth muscle cells (VSMC), while silencing Srebf1 exerts an opposite effect. Mechanistically, SREBP1-mediated lipogenesis upregulates acetyl-CoA pool to increase histone acetylation, modifying the chromatin accessibility which limiting recruitment of SRF/myocardin complexes to CArG boxes of contractile genes and opening the chromatin accessibility of aging genes. Srebf1 knockdown and local delivery of lentivirus or AAV-mediated VSMC specific expressing sh-Srebf1 significantly attenuates the senescence-like transformation of VSMC both in vitro and in vivo. Our findings reveal a previously unrecognized feature of SREBP1-mediated lipogenesis in vascular biology and SM-induced carotid artery remodeling.