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.

Biochemical Pharmacology
|February 10, 2022
PubMed

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.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.8K
Atherosclerosis I: Introduction01:30

Atherosclerosis I: Introduction

Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
147
Peripheral Artery Disease I: Introduction01:30

Peripheral Artery Disease I: Introduction

Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...
58
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.2K