Activated monocytes induce smooth muscle cell death: role of macrophage colony-stimulating factor and cell contact

Puvi N Seshiah1, Dean J Kereiakes, Sanjay S Vasudevan

  • 1Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, USA.

Circulation
|January 16, 2002
PubMed
Abstract

Insights

Monocytes and macrophage colony-stimulating factor (M-CSF) trigger vascular smooth muscle cell (VSMC) death. The drug abciximab, targeting the Mac-1 receptor, can prevent this process, offering potential therapeutic avenues for cardiovascular events.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Cellular Pathology

Background:

  • Plaque disruption is a key event in coronary thrombosis and acute coronary syndromes.
  • Loss of vascular smooth muscle cells (VSMCs) contributes to plaque instability.
  • Monocytes/macrophages (MMs) activated by macrophage colony-stimulating factor (M-CSF) are implicated in VSMC death.

Purpose of the Study:

  • To investigate the role of M-CSF-activated MMs in VSMC apoptosis.
  • To identify potential therapeutic targets for preventing M-CSF-induced VSMC death.

Main Methods:

  • VSMC apoptosis was quantified in the presence of MMs and/or M-CSF.
  • The effect of abciximab, tirofiban, eptifibatide, and an anti-CD-18 antibody on VSMC apoptosis was assessed.
  • MM-VSMC interaction and M-CSF concentration dependency were evaluated.

Main Results:

  • M-CSF-activated MMs significantly increased VSMC apoptosis compared to controls.
  • MM cell contact was essential for M-CSF-stimulated VSMC killing.
  • Abciximab, which binds Mac-1 on MMs, significantly reduced VSMC apoptosis.
  • Tirofiban and eptifibatide, which do not inhibit Mac-1, did not prevent VSMC apoptosis.

Conclusions:

  • Monocytes and M-CSF induce VSMC apoptosis.
  • Inhibitors of the Mac-1 receptor, such as abciximab, can antagonize this apoptotic process.
  • Targeting the Mac-1 pathway may offer a therapeutic strategy for acute coronary syndromes.

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