Correlation between increasing tissue ischemia and circulating levels of angiogenic growth factors in peripheral artery disease

Cytokine. 2018 Oct:110:24-28. doi: 10.1016/j.cyto.2018.04.012. Epub 2018 Apr 23.

Abstract

Introduction: The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades.

Methods: The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle-brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements.

Results: The levels of VEGF (P = 0.009) and HGF (P < 0.001) increased significantly as the ischaemic burden became more severe according to the Rutherford grades. PDGF behaved in opposite manner and declined along increasing Rutherford grades (P = 0.004). A significant, inverse correlations between Rutherford grades was detected as follows; VEGF (Pearson's correlation = 0.183, P = 0.004), HGF (Pearson's correlation = 0.253, P < 0.001), bFGF (Pearson's correlation = 0.169, P = 0.008) and PDGF (Pearson's correlation = 0.296, P < 0.001). In addition, VEGF had a clear direct negative correlation with ABI (Pearson's correlation -0.19, P = 0.009) and TP (Pearson's correlation -0.20, P = 0.005) measurements.

Conclusions: Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end-stage PAD.

Keywords: Angiogenic growth factors; HGF; PDGF; Peripheral arterial disease; VEGF; bFGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Fibroblast Growth Factor 2 / blood
  • Fibroblast Growth Factor 2 / metabolism
  • Hepatocyte Growth Factor / blood
  • Humans
  • Ischemia / blood*
  • Ischemia / metabolism*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / blood
  • Neovascularization, Pathologic / metabolism
  • Peripheral Arterial Disease / blood*
  • Peripheral Arterial Disease / metabolism*
  • Platelet-Derived Growth Factor / metabolism
  • Pressure
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factors / blood*
  • Vascular Endothelial Growth Factors / metabolism*

Substances

  • Platelet-Derived Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2
  • Hepatocyte Growth Factor