Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function

Figures

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  Figure 1. Soluble EPCR level in plasma: association with PAD severity and cardiovascular risk factors. (A), Levels of soluble endothelial protein receptor C (sEPCR) were determined in the plasma of patients with peripheral artery disease (PAD) stage II (n = 19; ●) and age- and sex-matched persons with cardiovascular risk factors and no PAD diagnosis (n = 19; ). The results of the statistical analysis (using Mann–Whitney test) are shown within the graph. (B), Plasma sEPCR levels in age- and sex-matched healthy persons with () and without (◯) cardiovascular risk factors and in sex-matched individuals 35 years of age or younger (□). The results of the statistical analysis (using Kruskall–Wallis, Dunn’s multiple comparisons test) are shown within the graph. (C), Comparison of plasma sEPCR levels in patients with PAD stage II (●) and stage III/IV (♦), examined within the same experiments. The results of the statistical analysis (using Mann–Whitney test) are shown within the graph. Simple linear regression analysis of the association of plasma sEPCR levels with the ankle-brachial index (D), age (E), body mass index (BMI; (F)), and plasma protein C activity (G) or ADAM17 levels (H) was performed.…

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  Figure 2. Plasma markers of endothelial dysfunction. Plasma levels of sE-selectin (A) and sTie2 (C) were measured in PAD stage II patients (●) and in age- and sex-matched healthy persons with () and without (◯) cardiovascular risk factors. The results of the statistical analysis (using One-Way-ANOVA, Sidak’s multiple comparisons test) are shown within the graph. Simple linear regression analysis of the association of plasma sEPCR and sE-selectin levels in age-matched person with risk factors (; (B)) or with sTie2 levels in PAD stage II patients (●; (D)). Simple linear regression analysis of the association of plasma sE-selectin (E) or sTie2 (F) levels with the ankle-brachial index, determined in PAD stage II patients (●). The r-squared and the p-values are shown within the graphs. Significant differences are highlighted in bold.

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  Figure 3. Biomarkers of inflammation and their association with sEPCR. (A), White blood cell (WBC) counts were determined in whole blood of PAD stage II patients (●) and in age- and sex-matched healthy persons with () and without (◯) cardiovascular risk factors. Plasma from these groups was also examined for the concentrations of high-sensitive C-reactive protein (hsCRP; (B)), tumor necrosis factor-alpha (TNFα; (C)), or interleukin-1beta (IL1β; (D)). The results of the statistical analysis ((A,C): One-Way-ANOVA, Sidak’s multiple comparisons test; (B,D): Kruskall–Wallis, Dunn’s multiple comparisons test) are shown within the graph. Simple linear regression analysis of the association of sEPCR and hsCRP levels in plasma (E) or with the white blood cell count in whole blood (F). In sex-matched individuals 35 years of age or younger (□). The r-squared and the p-values are shown within the graphs. Significant differences are highlighted in bold.

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  Figure 4. Plasma levels of angiogenic growth factors and relation with endothelial function. Plasma levels of vascular endothelial growth factor (VEGF; A) and active transforming growth factor-beta (TGFβ1; (B)) were determined in PAD stage II patients (●) and in age- and sex-matched healthy persons, with () and without (◯) cardiovascular risk factors. The results of the statistical analysis (A: Kruskall–Wallis, Dunn’s multiple comparisons test; B: One-Way ANOVA, Sidak’s multiple comparisons test) are shown within the graph. Simple linear regression analysis to determine the association of VEGF (C) or active TGFβ1 (D) with sE-selectin levels in plasma of PAD stage II patients (●) and in age- and sex-matched healthy persons, with () and without (◯) cardiovascular risk factors, and of plasma VEGF (E) or active TGFβ1 (F) and the ankle-brachial index (in PAD stage II patients only). The r-squared and the p-values are shown within the graphs. Significant differences are highlighted in bold.