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Angiotensin II-induced MMP-2 release from endothelial cells is mediated by TNF-alpha

Ivan A Arenas1, Yi Xu, Patricio Lopez-Jaramillo

  • 1Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada T6G 2S2.

American Journal of Physiology. Cell Physiology
|December 3, 2003
PubMed

Insights

Angiotensin II (ANG II) increases tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-2 (MMP-2) in endothelial cells, contributing to vascular disease. TNF-alpha mediates ANG II

Area of Science:

  • Cardiovascular Biology
  • Endothelial Cell Function
  • Molecular Medicine

Background:

  • Angiotensin II (ANG II) is implicated in vascular disease, but its precise role in endothelial dysfunction remains unclear.
  • Matrix metalloproteinases (MMPs) and proinflammatory cytokines are key factors in vascular pathological remodeling.
  • Understanding ANG II's impact on endothelial cells is crucial for addressing vascular disorders.

Purpose of the Study:

  • To investigate the effects of ANG II on tumor necrosis factor-alpha (TNF-alpha) and MMP-2 production in human umbilical vein endothelial cells (HUVECs).
  • To determine the role of ANG II receptors (AT(1)R and AT(2)R) in mediating these effects.
  • To elucidate the potential involvement of TNF-alpha in ANG II-induced MMP-2 release.

Main Methods:

  • HUVECs were stimulated with ANG II in the presence or absence of AT(1)R and AT(2)R antagonists.
  • TNF-alpha and MMP-2 production and release were assessed using molecular and biochemical assays.
  • The role of endogenous TNF-alpha was evaluated using neutralizing antibodies and inhibitors.

Main Results:

  • ANG II significantly increased TNF-alpha mRNA and protein expression and its bioactive release.
  • ANG II stimulated MMP-2 release and decreased tissue inhibitor of MMP (TIMP)-2 secretion.
  • Inhibition of TNF-alpha производство prevented ANG II-induced MMP-2 secretion.
  • AT(1)R antagonism abolished the effects of ANG II on TNF-alpha, MMP-2, and TIMP-2.

Conclusions:

  • ANG II, acting through the AT(1)R, modulates TNF-alpha and MMP-2 secretion in endothelial cells.
  • TNF-alpha acts as a mediator for ANG II's effects on MMP-2 release.
  • These findings highlight a novel mechanism linking ANG II signaling to endothelial dysfunction and vascular remodeling.

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