Profiling of main regulators of angiogenesis and inflammation in human PBMC and plasma revealed associations with lower extremity artery disease

Lower extremity artery disease (LEAD) represents the most common atherosclerosis-related disease in the group of peripheral artery diseases. A growing amount of evidence suggests that dysregulations in signaling pathways associated with angiogenesis and inflammation can contribute to the progression and onset of LEAD; however, this association is still poorly understood. Therefore, in our study, we investigated expression levels of 18 genes that encode key regulators of angiogenesis and inflammation, as well as plasma levels of their protein products, in patients with LEAD in comparison with non-LEAD controls. Gene expression levels were determined in peripheral blood mononuclear cells (PBMC) using real-time PCR, and protein plasma levels were measured using ELISA. The expression levels of TGFB1, VEGFA, and VEGFB, as well as the plasma concentrations of ANG-1, CCL2, PDGF-AB, TGF-beta 1, and TNF-alpha, significantly differentiated the LEAD group from the control group. A strong correlation was found between the expression levels of TGFB1 and VEGFA. Significant relationships between VEGFB expression and blood cholesterol levels, as well as between CCL2 plasma concentrations and C-reactive protein blood levels, were demonstrated. Identified dysregulations in key angiogenesis and inflammation-related factors could reflect abnormal regulation of these processes in patients with LEAD, shedding new light on the molecular mechanisms underlying the development of LEAD and indicating candidates for circulatory biomarkers of this disease.