Major mechanisms involved in the etiopathogenesis of aPL-mediated clinical events4,55
| Mechanisms and examples of aPL-induced proinflammatory/thrombotic changes . |
|---|
| Cell activation |
| Endothelial cells |
| ↑ TF production |
| ↑ E-selectin, P-selectin, VCAM-1, and I-CAM-1 expression |
| ↑ MCP-1 expression |
| ↑ Leukocyte-endothelium interaction |
| ↑ mTOR pathway activity |
| ↓ eNOS production |
| ↑ Release of microparticles |
| Platelets |
| ↑ Expression of TxA2/B2 |
| ↑ Expression of GPIIb/IIIa |
| Monocytes |
| ↑ TF production |
| ↑ TNF-α and IL-1β expression |
| ↑ VEGF and its receptor expression |
| Neutrophils |
| ↑ TF production |
| ↑ IL-8 production |
| ↑ Release of neutrophil extracellular traps |
| ↑ Oxidative stress |
| ↑ Levels of circulating LDGs |
| Complement activation |
| ↑ “Classical” and “alternative” complement pathway activity |
| ↑ TF production |
| Coagulation system activation |
| ↑ TF activation |
| ↓ TF pathway inhibition |
| ↓ Annexin A5 anticoagulation shield |
| ↑ Prothrombin binding |
| ↓ Antithrombin activity |
| ↑ Activated protein C resistance |
| ↓ Fibrinolysis |
| Mechanisms and examples of aPL-induced proinflammatory/thrombotic changes . |
|---|
| Cell activation |
| Endothelial cells |
| ↑ TF production |
| ↑ E-selectin, P-selectin, VCAM-1, and I-CAM-1 expression |
| ↑ MCP-1 expression |
| ↑ Leukocyte-endothelium interaction |
| ↑ mTOR pathway activity |
| ↓ eNOS production |
| ↑ Release of microparticles |
| Platelets |
| ↑ Expression of TxA2/B2 |
| ↑ Expression of GPIIb/IIIa |
| Monocytes |
| ↑ TF production |
| ↑ TNF-α and IL-1β expression |
| ↑ VEGF and its receptor expression |
| Neutrophils |
| ↑ TF production |
| ↑ IL-8 production |
| ↑ Release of neutrophil extracellular traps |
| ↑ Oxidative stress |
| ↑ Levels of circulating LDGs |
| Complement activation |
| ↑ “Classical” and “alternative” complement pathway activity |
| ↑ TF production |
| Coagulation system activation |
| ↑ TF activation |
| ↓ TF pathway inhibition |
| ↓ Annexin A5 anticoagulation shield |
| ↑ Prothrombin binding |
| ↓ Antithrombin activity |
| ↑ Activated protein C resistance |
| ↓ Fibrinolysis |
eNOS, endothelial nitric oxide synthetase; GPIIb/IIIa, glycoprotein IIb/IIIa; I-CAM-1, intracellular adhesion molecule 1; IL-8, interleukin-8; LDG, low-density granulocyte; MCP-1, monocyte chemoattractant protein 1; mTOR, mammalian target of rapamycin; TF, tissue factor; TNF-α, tumor necrosis factor-α; TxA2/B2, thromboxane A2/B2; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor.