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LSD1 downregulates p21 expression in vascular smooth muscle cells and promotes neointima formation
Baohui Yuan1, He Liu1, Xiaohua Pan1
1Wuxi School of Medicine and School of Food Science and Technology, Jiangnan University, Wuxi, China.
Abstract:
Neointima formation is characterized by the proliferation of vascular smooth muscle cells (VSMC). Although lysine-specific demethylase 1 (LSD1) has critical functions in several diseases, its role in neointima formation remains to be clarified. In this study, we aimed to explore the crucial role of LSD1 on neointima formation using a carotid artery injury model in mice. We observed that aberrant LSD1 expression was increased in human and mouse stenotic arteries and platelet-derived growth factor-BB (PDGF-BB)-treated VSMC. Furthermore, LSD1 knockdown significantly mitigated neointima formation in vivo and inhibited PDGF-BB-induced VSMC proliferation in vitro. We further uncovered that LSD1 overexpression exhibited opposite phenotypes in vivo and in vitro. Finally, LSD1 knockdown inhibited VSMC proliferation by increasing p21 expression, which is associated with LSD1 mediated di-methylated histone H3 on lysine 4 (H3K4me2) modification. Taken together, our data suggest that LSD1 may be a potential therapeutic target for the treatment of neointima formation.
Insights
Lysine-specific demethylase 1 (LSD1) promotes vascular smooth muscle cell proliferation and neointima formation. Inhibiting LSD1 may offer a new therapeutic strategy for treating artery stenosis.
Area of Science:
- Vascular Biology
- Epigenetics
- Cell Biology
Background:
- Neointima formation, driven by vascular smooth muscle cell (VSMC) proliferation, is a key factor in artery stenosis.
- The role of lysine-specific demethylase 1 (LSD1) in neointima formation is not well understood.
Purpose of the Study:
- To investigate the role of LSD1 in neointima formation.
- To explore LSD1 as a potential therapeutic target for artery stenosis.
Main Methods:
- Utilized a mouse carotid artery injury model for in vivo studies.
- Employed platelet-derived growth factor-BB (PDGF-BB) to stimulate VSMC proliferation in vitro.
- Assessed LSD1 expression, VSMC proliferation, and histone modifications (H3K4me2) following LSD1 modulation.
Main Results:
- LSD1 expression was elevated in stenotic arteries and PDGF-BB-treated VSMCs.
- LSD1 knockdown reduced neointima formation in vivo and VSMC proliferation in vitro.
- LSD1 knockdown increased p21 expression, linked to LSD1-mediated H3K4me2 demethylation.
Conclusions:
- LSD1 plays a critical role in promoting VSMC proliferation and neointima formation.
- LSD1 inhibition represents a promising therapeutic approach for treating artery stenosis.
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