*5.1.1.1 Endothelial-derived EVs*

The endothelium is the major player in APS pathogenesis, so it is not surprising that endothelial EVs have been the most extensively studied (**Table 2**). Combes et al. published in 1999 the first study investigating endothelial EVs in APS using flow cytometry to detect endothelial marker integrin CD51+ EVs. They showed increased levels of endothelial EVs in LA+ patients compared to HBDs [53]. In addition, they have also showed a significant increase in endothelial EVs in LA+ patients with a history of thrombosis compared to asymptomatic LA+ patients. On the other hand, Jy et al. found no difference in endothelial EVs (CD31+/CD42-) between aPL+ thrombotic patients and asymptomatic aPL+ group, suggesting that the release of EVs might be related to the autoimmune process involving the presence of aPL [88]. Dignat-George et al. in 2004, showed increased levels of CD51+ endothelial EVs in APS patients and in aPL+ SLE patients compared to HBDs [87]. Increased levels of endothelial EVs were observed in aPL+ patients vs. HBDs as well as in aPL+ patients vs. aPL- patients. Increased levels of endothelial EVs in the plasma of APS patients compared to HBDs were later confirmed also in several other studies [90, 93, 94] (**Table 2**), in which different endothelial surface markers (CD31+, CD51+, CD105+, CD144+) were examined. Levels of endothelial EVs were shown to be increased in APS patients with exception of one study where the increase was not observed [89]. Chaturvedi et al., on the other hand investigated levels of TF+ endothelial EVs, and found them to be elevated in aPL+ patients, compared to HBDs [92]. A higher TF activity was also observed when comparing APS patients with asymptomatic aPL+ patients [91]. Contrarily, Hell et al. could not observe increased TF activity of endothelial EVs in APS patients vs. HBDs.

## *5.1.1.2 Monocyte- and Platelet-derived EVs*

Platelet-derived EVs are the most numerous type of vesicles found in the circulation of healthy individuals [96], and their levels are further increased in disease [38]. They are known to play key roles in coagulation, thrombosis, vascular senescence and permeability. It has been suggested that platelet EVs induce vascular dysfunction and influence immune modulation, leading to vascular remodeling. Monocytes contribute to APS pathogenesis also by being the main source of tissue factor, which is one of the key initiators of the coagulation cascade. Similar to platelet EVs, it has been suggested that monocyte EVs cooperate in coagulation and vascular inflammation [38]. However, in APS, monocyte EVs (**Table 2**) have been less extensively studied compared to endothelial EVs. Joseph et al., showed no difference in plasma levels of

### *Extracellular Vesicles: Intercellular Communication Mediators in Antiphospholipid Syndrome DOI: http://dx.doi.org/10.5772/intechopen.97412*

CD41+ platelet EVs between APS patients and HBDs [85]. This is consistent with the study by Vikenfors et al. (CD42a+) [97] and by Nascimento et al. (CD61+) [89]. On the other hand, increased levels of platelet EVs (CD41+, CD41a+, CD42+, CD42a+) were found in five other studies [86, 88, 92–94]. Jy et al. have shown an increase in platelet EVs in APS patients vs. asymptomatic aPL+ suggesting thrombosis rather than aPL may play a role in platelet EVs release [88]. An increase in monocyte EVs in APS patients compared to HBDs was observed by Nagahama et al. and Vikenfors et al. which is in contrast to two other studies where the authors could not see an increase [89, 92]. There is no consensus on whether platelet and monocyte EVs are elevated in APS patients and there is too little data to conclude on the effects of these EVs in APS patients.
