Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: a link between angiogenesis and thrombogenesis?

Abstract

Increasing evidence points towards a prothrombotic state in atherosclerosis and its manifestations, such as peripheral artery disease (PAD), which is associated with thrombosis-related complications, such as acute limb ischaemia, graft thrombosis and stroke. We hypothesized that the increased risk of thrombogenesis in PAD may be related to abnormal angiogenesis and, thus, an increased risk of future vascular disease. To test this hypothesis, we measured plasma levels of tissue factor (TF) and related levels to indices of angiogenesis, that is vascular endothelial growth factor (VEGF) and its soluble receptor sFlt-1. We studied 234 patients (145 males; mean age 68.6±10 years) with proven PAD (ankle brachial pressure index <0.8) and compared them with 50 healthy controls. Levels of VEGF (P = 0.001) and TF (P = 0.043) were increased in patients compared with controls. There were significant correlations between VEGF and TF levels in both patients (Spearman r = 0.351, P<0.001) and healthy controls (Spearman r = 0.335, P = 0.017). Amongst PAD patients, levels of VEGF were related to gender, with women having higher levels than men. There was no difference in the levels of sFlt-1 between the patients and controls, or between the subgroups of patients. There were however significant correlations between the levels of sFlt-1 and TF (Spearman r = 0.268, P<0.001) and between sFlt-1 and VEGF (Spearman r = 0.499, P<0.001). In conclusion, patients suffering from proven PAD have higher plasma levels of TF and VEGF compared with controls, with a significant correlation between the two. This suggests a link between the hypercoagulable state in PAD and the process of angiogenesis.