LSD1 downregulates p21 expression in vascular smooth muscle cells and promotes neointima formation

Baohui Yuan; He Liu; Xiaohua Pan; Xiaoliang Dong; Le-Feng Qu; Jia Sun; Li-Long Pan

doi:10.1016/j.bcp.2022.114947

LSD1 downregulates p21 expression in vascular smooth muscle cells and promotes neointima formation

Biochem Pharmacol. 2022 Apr:198:114947. doi: 10.1016/j.bcp.2022.114947. Epub 2022 Feb 7.

Authors

Baohui Yuan¹, He Liu¹, Xiaohua Pan¹, Xiaoliang Dong¹, Le-Feng Qu², Jia Sun³, Li-Long Pan⁴

Affiliations

¹ Wuxi School of Medicine and School of Food Science and Technology, Jiangnan University, Wuxi, China.
² Department of Vascular and Endovascular Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China. Electronic address: qulefeng@smmu.edu.cn.
³ Wuxi School of Medicine and School of Food Science and Technology, Jiangnan University, Wuxi, China. Electronic address: jiasun@jiangnan.edu.cn.
⁴ Wuxi School of Medicine and School of Food Science and Technology, Jiangnan University, Wuxi, China. Electronic address: llpan@jiangnan.edu.cn.

PMID: 35143753
DOI: 10.1016/j.bcp.2022.114947

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.

Keywords: Lysine-specific demethylase 1; Neointima formation; P21; Vascular smooth muscle cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Becaplermin / metabolism
Becaplermin / pharmacology
Carotid Artery Injuries* / genetics
Carotid Artery Injuries* / metabolism
Cell Movement
Cell Proliferation
Cells, Cultured
Histone Demethylases* / genetics
Histone Demethylases* / metabolism
Humans
Lysine / metabolism
Mice
Muscle, Smooth, Vascular / cytology
Myocytes, Smooth Muscle* / metabolism
Neointima* / metabolism

Substances

Becaplermin
Histone Demethylases
KDM1a protein, mouse
KDM1A protein, human
Lysine