Frontiers in Pharmacology (Jan 2022)

Deletion of Smooth Muscle Lethal Giant Larvae 1 Promotes Neointimal Hyperplasia in Mice

  • Ya Zhang,
  • Peidong Yuan,
  • Peidong Yuan,
  • Xiaoping Ma,
  • Qiming Deng,
  • Jiangang Gao,
  • Jianmin Yang,
  • Tianran Zhang,
  • Cheng Zhang,
  • Wencheng Zhang,
  • Wencheng Zhang

DOI
https://doi.org/10.3389/fphar.2022.834296
Journal volume & issue
Vol. 13

Abstract

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Vascular smooth muscle cell (VSMC) proliferation and migration contribute to neointimal hyperplasia after injury, which causes vascular remodeling related to arteriosclerosis, hypertension, and restenosis. Lethal giant larvae 1 (LGL1) is a highly conserved protein and plays an important role in cell polarity and tumor suppression. However, whether LGL1 affects neointimal hyperplasia is still unknown. In this study, we used smooth muscle-specific LGL1 knockout (LGL1SMKO) mice generated by cross-breeding LGL1flox/flox mice with α-SMA-Cre mice. LGL1 expression was significantly decreased during both carotid artery ligation in vivo and PDGF-BB stimulation in vitro. LGL1 overexpression inhibited the proliferation and migration of VSMCs. Mechanistically, LGL1 could bind with signal transducer and activator of transcription 3 (STAT3) and promote its degradation via the proteasomal pathway. In the carotid artery ligation animal model, smooth muscle-specific deletion of LGL1 accelerated neointimal hyperplasia, which was attenuated by the STAT3 inhibitor SH-4-54. In conclusion, LGL1 may inhibit neointimal hyperplasia by repressing VSMC proliferation and migration via promoting STAT3 proteasomal degradation.

Keywords