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Vascular endothelial growth factor modified macrophages transdifferentiate into endothelial-like cells and decrease

Dan Yan1, Yujuan He2, Jun Dai3

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Overexpressing vascular endothelial growth factor (VEGF) in macrophages transforms them into endothelial-like cells, promoting vascular repair and inhibiting foam cell formation in atherosclerosis treatment.

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Area of Science:

  • Cardiovascular Biology
  • Cell Biology
  • Immunology

Background:

  • Macrophages play a crucial role in atherosclerosis development, contributing to lesion initiation and progression.
  • Foam cell formation by macrophages is a key pathological feature of atherosclerosis.
  • Strategies to inhibit macrophage dysfunction are vital for preventing atherosclerosis.

Purpose of the Study:

  • To investigate whether overexpressing endogenous human vascular endothelial growth factor (VEGF) can induce macrophages to transdifferentiate into endothelial-like cells (ELCs).
  • To determine if VEGF-modified macrophages can inhibit foam cell formation.
  • To explore the therapeutic potential of VEGF-modified macrophages in atherosclerosis.

Main Methods:

  • Macrophages were genetically modified to stably overexpress human VEGF (hVEGF165).
  • Transdifferentiation capability into ELCs was assessed in vitro.
  • Foam cell formation was evaluated by measuring cytoplasmic lipid accumulation after exposure to oxidized LDL (ox-LDL).
  • CD36 expression levels were analyzed.

Main Results:

  • VEGF-modified macrophages demonstrated a high capacity for transdifferentiation into ELCs in vitro.
  • Endogenous VEGF, but not exogenous VEGF, induced this transdifferentiation.
  • VEGF-modified macrophages showed significantly reduced lipid accumulation upon ox-LDL treatment.
  • Down-regulation of CD36 expression was observed, potentially contributing to reduced foam cell formation.

Conclusions:

  • VEGF-modified macrophages can be atheroprotective by promoting vascular repair through transdifferentiation into ELCs.
  • These modified macrophages inhibit foam cell formation, a hallmark of atherosclerosis.
  • VEGF-modified macrophages represent a promising cell-based therapy for atherosclerosis.