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.
Highlights
The 77 patients with lower extremity artery disease (LEAD) (average age (63.4± 8.8) years) included 62 with intermittent claudication (IC) and 15 with critical limb ischemia (CLI)
The concentrations of vascular endothelial growth factor A (VEGF-A), sVEGFR-1, sVEGFR-2, matrix metalloproteinase 2 (MMP-2), MMP-9, TIMP-1, and TIMP-2 were measured in plasma obtained from venous blood specimens using an enzyme-linked immunosorbent assay (ELISA; R&D Systems, USA)
The sVEGFR-1/VEGF-A and sVEGFR-2/VEGF-A ratios were insignificantly higher in patients with IC compared to the patients with CLI, which suggested that the patients with CLI had the lowest inhibition of angiogenesis and the highest VEGF-A concentration
Summary
A negative correlation was identified between MMP-9 concentrations and the absolute claudication distance (R=−0.27; P=0.02), and the number of packyears and TIMP-1 (R=−0.26; P=0.02). The correlations between MMP-2, MMP-9, and angiogenesis parameters in patients with CLI are difficult to clearly explain, since MMPs participate in the development of artery disease, especially in the progression of the atherosclerotic plaque and a compensation response to ischemia and hypoxia that includes angio- and arteriogenesis (Hobeika et al, 2008; Busti et al, 2010) This can be reflected in high gene expression at the mRNA level that has been observed for MMPs (MMP-9) and VEGF-A in subjects with CLI using popliteal artery samples collected during amputation (Baczynska et al, 2016). In subjects with CLI, high concentrations of VEGF-A were accompanied by elevated levels of MMP-9, TIMP-1, and TIMP-2, which confirms the interaction of proangiogenic factors and MMPs. Radosław WIECZÓR and Danuta ROŚĆ performed the experimental research and data analysis, wrote and edited the manuscript. All authors read and approved the final manuscript and, had full access to all the data in the study and take responsibility for the integrity and security of the data
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