Fig. 6 | Nature Communications

Fig. 6

From: Adenosine receptor agonism protects against NETosis and thrombosis in antiphospholipid syndrome

Fig. 6

Agonism of the adenosine A2A receptor mitigates venous thrombosis in APS mice. a–d Thrombus incidence (b), thrombus weight (c), and thrombus length (d) were assessed for mice subjected to the flow-restriction model (a). Here, mice were additionally treated with APS IgG as described in Methods. Each data point represents a unique mouse, while horizontal lines denote mean values; **p < 0.01 and ***p < 0.001 as compared with the control group (Chi-square test for panel b and unpaired t-test for panels c, d). e Schematic of the electrolytic model of venous thrombosis. Direct current results in the release of free radicals within the IVC, which activate endothelial cells and initiate a thrombogenic environment in the presence of constant blood flow. Thrombus formation was assessed at 24 h for all of the following experiments. f, g Thrombus size (f) and representative thrombi (g) for mice treated with control IgG or APS IgG as indicated. In this experiment, APS-1 through −4 represent unique patients. Each data point represents a unique mouse, while horizontal lines denote mean values; **p < 0.01 and ***p < 0.001 as compared with the control group by one-way ANOVA corrected with Dunnett’s test. The ruler denotes millimeters. h, i Thrombus size and plasma MPO-DNA complexes were determined for mice treated with various combinations of control IgG, APS IgG, and intravenous deoxyribonuclease (DNase) as indicated; ***p < 0.001 and ****p < 0.0001 as indicated by one-way ANOVA corrected with Sidak’s test (h) or Dunnett’s test (i). j, k Thrombus size and plasma MPO-DNA complexes were determined for mice treated with various combinations of APS IgG, CGS21680, and DNase as indicated; *p < 0.05, **p < 0.01, and ****p < 0.0001 as compared with the control group by one-way ANOVA corrected with Dunnett’s test. l, m Thrombus size and plasma MPO-DNA complexes were determined for mice treated with various combinations of APS IgG, dipyridamole, and DNase as indicated; *p < 0.05 and ***p < 0.001 as compared with the control group by one-way ANOVA corrected with Dunnett’s test

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