Coexistence of proangiogenic potential and increased MMP-9, TIMP-1, and TIMP-2 levels in the plasma of patients with critical limb ischemia

J Zhejiang Univ Sci B. 2019;20(8):687-692. doi: 10.1631/jzus.B1800373.

Abstract

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.

Keywords: Intermittent claudication; Critical limb ischemia; Vascular endothelial growth factor; Metalloproteinase.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / pharmacology
  • Female
  • Gene Expression Regulation
  • Humans
  • Intermittent Claudication / blood*
  • Intermittent Claudication / drug therapy
  • Ischemia / blood*
  • Ischemia / drug therapy
  • Lower Extremity / blood supply*
  • Male
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Neovascularization, Pathologic*
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Tissue Inhibitor of Metalloproteinase-2 / blood*
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-1 / blood
  • Vascular Endothelial Growth Factor Receptor-2 / blood

Substances

  • Angiogenesis Inhibitors
  • TIMP1 protein, human
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Tissue Inhibitor of Metalloproteinase-2
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9