Lycorine hydrochloride reveals a novel role in preventing neointimal hyperplasia through MAPK-mediated phenotypic switching of smooth muscle cells

  • J Mol Cell Cardiol. 2026 Jun:215:66-79. doi: 10.1016/j.yjmcc.2026.04.008.
Dongxu Li  1 ,  Li Li  1 ,  Yingying Fan  2 ,  Caiyun Lu  1 ,  Nan Feng  3 ,  Chaowei Zhang  1 ,  Ji Gao  1 ,  Siyu Sun  1 ,  Xiulong Wang  1 ,  Xuefang Li  1 ,  Libo Wang  1 ,  Zhigang Chen  4 ,  Guoan Zhao  5 ,  Fei Lin  6
Affiliations
  • 1. Heart Center, The First Affiliated Hospital of Xinxiang Medical University, 453100 Xinxiang, China; Henan Joint International Research Laboratory of Cardiovascular Injury and Repair, 453100 Xinxiang, China.
  • 2. Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, 453100 Xinxiang, China.
  • 3. Catheter Room, The First Affiliated Hospital of Xinxiang Medical University, 453100 Xinxiang, China.
  • 4. Henan Joint International Research Laboratory of Cardiovascular Injury and Repair, 453100 Xinxiang, China; Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, 453100 Xinxiang, China. Electronic address: [email protected].
  • 5. Heart Center, The First Affiliated Hospital of Xinxiang Medical University, 453100 Xinxiang, China; Henan Joint International Research Laboratory of Cardiovascular Injury and Repair, 453100 Xinxiang, China; Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, 453100 Xinxiang, China. Electronic address: [email protected].
  • 6. Heart Center, The First Affiliated Hospital of Xinxiang Medical University, 453100 Xinxiang, China; Henan Joint International Research Laboratory of Cardiovascular Injury and Repair, 453100 Xinxiang, China; Department of Traditional Chinese Medicine, The First Affiliated Hospital of Xinxiang Medical University, 453100 Xinxiang, China. Electronic address: [email protected].
PMID: 42061807 DOI: 10.1016/j.yjmcc.2026.04.008
Abstract

Neointimal hyperplasia results from irregular vascular smooth muscle cell (VSMC) proliferation and migration. Lycorine hydrochloride (LH), known for its cardioprotective properties, was investigated for its impact on neointimal hyperplasia and underlying mechanisms. In a murine model of left common carotid artery ligation (CAL)-induced neointimal hyperplasia, LH was administered intraperitoneally for 28 days. Further studies investigated LH's impact on MOVAS cells phenotype switching activated by platelet-derived growth factor-BB (PDGF-BB). LH significantly inhibited neointimal hyperplasia in vivo and decreased PDGF-BB-stimulated MOVAS cell proliferation, migration, inflammation and phenotypic transformation in vitro. Mechanistically, LH inhibited PDGF-BB-induced phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK1/2), c-Jun terminal kinase (c-Jun), and p38 MAP kinase (p38). Specific inhibitors (PD98059, SP600125, SB203580) diminished PDGF-BB-mediated MOVAS cell phenotypic switching, the potential mechanism involves binding to ERK1 to repress ERK1/2 activation. Therefore, LH suppressed PDGF-BB-mediated VSMCs phenotypic switching and attenuated vascular neointimal hyperplasia at least in part by targeting Ekr1 to regulate the MAPK cascade, indicating its potential as a prevention for restenosis.

Keywords
Lycorine hydrochloride; MAPKs; Neointimal hyperplasia; Phenotypic switching; Vascular smooth muscle cells.
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