Table 2.

Findings in animal models of thrombosis.

EV Type	Model	Species	Main Findings
Arterial thrombosis
MPs	Laser-induced endothelial injury of arterioles in cremaster muscle	C57BL/6J, B6.Cg-SelPltm1Fur and C57BL/6J-Selptm1Bay mice	Interaction of TF-positive EVs with thrombi occurs through the interaction of PSGL-1 expressed on microparticles and P-selectin expressed on platelets [94]
MPs	FeCl3-induced injury of carotid artery	C57BL/6J and CD36−/− mice	PS-exposing MPs released from activated platelets bind to CD36 receptor on platelets which results in enhanced platelet activation and thrombus formation [227]
MPs	Wire-induced endothelial denudation of carotid artery	Swiss mice	MPs isolated from stored murine platelet concentrates adhere on the vascular wall through an integrin aIIbβ3-mediated mechanism [94]
EVs	Rose Bengal-induced carotid artery injury	C57BL/6J and miR-223−/− mice	Platelet-derived EVs accelerate arterial thrombus formation by transferring miR-223 and downregulating IGFR-1 on endothelial cells [229]
Tumor exosomes	Tandem stenosis at the carotid artery	C57BL/6J WT and apoE−/− mice	Elevated plasma exosomal miR-223, miR-339 and miR-21 levels in mice following induction of atherothrombosis [246]
Venous thrombosis
MPs	IVC ligation	C57BL/6J, CD62E−/−, CD62P−/− and Delta Cytoplasmic Tail mice	MPs derived from platelets and leukocytes correlate with venous thrombus weight MP re-injection leads to higher thrombus weight than IVC alone, TF on MPs correlates to MP numbers [232]
MPs	IVC ligation	C57BL/6, CD62P−/− and CD62E−/− mice	An association between platelet-MPs and venous thrombus weight was observed in mice lacking P- or E-selectin [233]
MPs	IVC ligation	C57BL/6J, CD62E−/−, CD62P−/− and Delta Cytoplasmic Tail mice	High circulating levels of soluble P-selectin and leucocyte MPs are associated with increased venous thrombosis. Antibodies directed against PSGL-1 decreased thrombus mass [234]
MPs	IVC ligation/stasis	Wistar Hsd/Cpb; WU rats	Human cell-derived microparticles promote venous thrombus formation in a tissue factor-dependent manner [93]
MPs	IVC ligation/stasis	Rats	MPs from IL1α-stimulated endothelial MPs promote venous thrombus formation, and thrombus weight is significantly reduced by anti-TF, but not by anti-Factor XII antibodies [36]
TF+ tumor EVs	IVC ligation/stenosis	Nude mice	EVs from TF-overexpressing human ovarian cancer cells enhance murine venous thrombus formation [236]
TF+ tumor MPs	IVC ligation/stenosis	Nude mice	Thrombus weight does not differ between human pancreatic tumor-bearing and control mice, whereas injection of TF+ MPs dose-dependently increases venous thrombosis [237]
TF+ tumor MPs	IVC ligation	Nude mice	Venous clots are larger in mice bearing tumors compared to controls [239]
Tumor MPs	Laser and FeCl3 injury, cremaster and mesentery	C57BL/6J mice	Mice with tumors have larger thrombi, and infusion of a blocking P-selectin antibody abolishes the thrombotic state observed after injection of MPs or in mice developing a tumor [240]
Tumor MPs	IVC ligation/particle flow restriction	C57BL/6J mice	Larger venous thrombi in tumor-bearing mice or mice injected with high TF tumor MPs having more pronounced effects than low TF tumor MPs [240]
TF+ tumor MPs	Femoral and IVC ligation	C57BL/6J and PAR4−/− mice	TF-positive MPs obtained from human pancreatic adenocarcinoma expressing low or high TF levels enhance venous thrombosis in two mouse models. Reduced thrombosis in PAR4−/− mice and in mice treated with clopidogrel suggested role of platelets [243]
TF+ tumor MPs	Laser injury cremaster muscle	C57BL/6J mice	Inhibition of platelet activation reduces integrin αvβ1 and αvβ3 dependent accumulation of cancer cell MPs and thrombosis in human pancreatic tumor-bearing mice [244]
Tumor exosomes	Rose Bengal venous thrombosis	BALB/c mice	Intravenous administration of 4T1-derived exosomes enhances NET formation and venous thrombosis in mice treated with G-CSF [245]