Angiogenesis, thrombogenesis, endothelial dysfunction and angiographic severity of coronary artery disease

Abstract

Background: Thrombogenesis, angiogenesis, and endothelial damage/dysfunction are components in the pathogenesis of atherosclerosis. Objective: To investigate the relation of these variables to atherosclerotic disease severity and the possible interrelations between the three. Methods: 111 patients attending for coronary angiography were studied (85 male, 26 female; mean (SD) age, 61.6 (10.0) years). Plasma concentrations of von Willebrand factor (vWf, a marker of endothelial damage/dysfunction), vascular endothelial growth factor (VEGF, associated with angiogenesis), soluble VEGF receptor Flt-1 (sFlt-1), and tissue factor (TF, a key component of coagulation) were measured by an enzyme linked immunosorbent assay. Following angiography, disease severity was assessed by the number of coronary vessels diseased (> 50% stenosis) and by a coronary atheroma score. Results: All indices were raised in the patients compared with 34 healthy controls except sFlt-1, which was lower in the patients. No significant correlations were found between the coronary atheroma score and values of vWf (Spearman correlations: r = 0.21, p = 0.83), VEGF (r = 0.11, p = 0.27), or TF (r = -0.04, p = 0.68). However, there was an inverse correlation between plasma sFlt-1 and coronary atheroma score (r = -0.19, p = 0.049). The number of vessels diseased had no relation to any marker. Correlations were found between TF and VEGF (r = 0.25, p = 0.008) and between TF and sFlt-1 (r = 0.42, p < 0.001) in the patients. Conclusions: Despite evidence of abnormal angiogenesis (VEGF and sFlt-1), thrombogenesis (TF), and endothelial damage/dysfunction (vWf) in the patients with coronary artery disease, there was no correlation between VEGF, sFlt-1, vWf, or TF and angiographically defined disease severity.