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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.834296

DOI=10.3389/fphar.2022.834296

ISSN=1663-9812

ABSTRACT=<p>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 (LGL1<sup>SMKO</sup>) mice generated by cross-breeding LGL1<sup>flox/flox</sup> mice with α-SMA-Cre mice. LGL1 expression was significantly decreased during both carotid artery ligation <italic>in vivo</italic> and PDGF-BB stimulation <italic>in vitro</italic>. 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 <italic>via</italic> 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 <italic>via</italic> promoting STAT3 proteasomal degradation.</p>