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Tissue factor pathway inhibitor gene transfer prevents vascular smooth muscle cell proliferation by interfering with

Yu Fu1, Dandan Ma1, Yue Liu1

  • 1Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Laboratory Investigation; a Journal of Technical Methods and Pathology
|August 25, 2015
PubMed

Insights

Monocyte chemotactic protein-3 (MCP-3) promotes vascular smooth muscle cell (VSMC) proliferation. Tissue factor pathway inhibitor (TFPI) gene transfer inhibits this proliferation by blocking the MCP-3/CCR2 pathway, offering a potential therapy for atherosclerosis.

Area of Science:

  • Vascular biology
  • Immunology
  • Molecular medicine

Background:

  • Vascular smooth muscle cell (VSMC) proliferation is a key factor in atherosclerosis and intimal hyperplasia.
  • Inflammation's role in VSMC proliferation is increasingly recognized as a therapeutic target.

Purpose of the Study:

  • To investigate the effect of monocyte chemotactic protein-3 (MCP-3) on TNF-α-induced VSMC proliferation.
  • To determine if tissue factor pathway inhibitor (TFPI) gene overexpression can prevent VSMC proliferation by inhibiting the MCP-3/CC chemokine receptor 2 (CCR2) pathway.

Main Methods:

  • In vitro study using mouse VSMCs infected with adenoviruses carrying MCP-3-shRNA or TFPI gene.
  • Cells were stimulated with TNF-α, and proliferation was assessed using BrdU ELISA and MTT assays.
  • Expression of MCP-3, CCR2, and phosphorylation of ERK1/2 and AKT were analyzed by ELISA and western blot.

Main Results:

  • MCP-3 and TFPI significantly decreased VSMC proliferation.
  • Both MCP-3-shRNA and TFPI inhibited MCP-3 and CCR2 expression.
  • TFPI suppressed ERK1/2 and PI3K/AKT signaling pathways, indicating an anti-proliferative role.

Conclusions:

  • MCP-3 is a pro-inflammatory factor that promotes VSMC proliferation.
  • TFPI exhibits an anti-proliferative effect in TNF-α-stimulated VSMCs by interfering with the MCP-3/CCR2 pathway.
  • TFPI gene transfer is a potential therapeutic strategy for atherosclerosis and intimal hyperplasia.

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