Table 1.

Detrimental and Favorable Effects of Extracellular Vesicles on Vascular Function

Effect	EV Type	Isolation Method	Donor Cell/Origin	In Vitro Experiment	In Vivo Experiment	Effects	Mechanisms	Ref. #
Detrimental effects
	Injured endothelial MVs	Centrifugation 20,000 g	Glucose-treated HCAECs	HCAECs	ApoE−/− mice	Induce EC inflammation	Up-regulate ICAM-1 and VCAM-1 in EC by activating p38	(33)
	Endothelial MVs	Ultracentrifugation 100,000 g	RMVECs	Aortic rings from rats	—	Impair vasorelaxation	Local oxidative stress	(41)
	Circulating MVs	Centrifugation 13,000 g	Patients with MI	Aortic rings from rats	—	Vasomotor dysfunction	Impair endothelial NO transduction pathway	(42)
	Erythrocyte MVs	Differential centrifugation	Human packed red blood cells under standard blood banking conditions	—	Rat vasoactivity models	Reduce vasoconstrictor effects	Degrade vasodilator NO	(45)
	Platelet exosomes	Ultracentrifugation 100,000 g	Platelets from septic patients	ECs	—	Induce ECs apoptosis	Superoxide; NO and peroxynitrite production	(46)
	PMN MVs	Ultracentrifugation 100,000 g	PMNs from healthy volunteers	HUVECs	—	Induce ECs activation	Stimulate EC cytokine release Induction of tissue factor	(53)
	Oxidized MVs	Ultracentrifugation 100,000 g	Oxidatively modified HUVECs	Monocytes	—	Stimulate monocytes adhesion to ECs	Contain oxidized phospholipids	(56)
	Plaque MVs	Centrifugation 20,500 g	Human atherosclerotic plaques	HUVECs	—	Promote inflammatory response	Carry catalytically activeTNF-alpha converting enzyme (TACE/ADAM17) Enhance the processing of TNF-α and TNF receptor	(70)
	Monocyte MVs	Ultracentrifugation 100,000 g	Human peripheral blood monocytes	VSMCs	—	Induce VSMCs cell death	Deliver cell death message via encapsulated caspase-1	(77)
	CD40 ligand plus plaque MPs	Centrifugation 20,500 g	Human atherosclerotic plaques	HUVECs	Wild-type and BalbC/Nude mice	Stimulate endothelial proliferation and angiogenesis	CD40L signaling	(82)
Favorable effects
	Endothelial apoptotic bodies	Centrifugation 16,000 g	HUVECs	HUVECs	Mice models of atherosclerosis	Promote atheroprotective effects Increase plaque stability Enhance progenitor cells recruitment	MiRNA-126-dependent inhibition of RGS16 Enhance CXCR4 and CXCL12	(27)
	Endothelial MVs	Centrifugation 20,000 g	HCAECs	HCAECs	—	Prevent HCAECs apoptosis	Annexin I/phosphatidylserine receptor–dependent inhibition of p38 activation	(96)
	Platelet MVs	Centrifugation 20,000 g	Platelets	EOCs	Mice models of arterial wire-induced injury	Enhance vasoregenerative potential of EOCs	Enhance EOCs recruitment, migration, differentiation Release proangiogenic factors	(97)
	Endothelial MVs	Centrifugation 20,000 g	HCAECs	HCAECs	Electric injury of murine carotid artery	Promote ECs migration and proliferation Accelerate re-endothelialization	Inhibit SPRED-1 via EMV-mediated transfer of miRNA-126	(103)
	Endothelial MVs	Centrifugation 20,000 g	HCAECs	VSMCs	Wire injury of murine carotid artery	Reduce neointima formation Diminished VSMCs proliferation and migration	Inhibit LRP6 via EMPs-mediated transfer of miRNA-126-3p	(104)
	Exosomes	Differential centrifugation	CMPCs	HMECs	—	Stimulate HMECs migration	EMMPRIN-mediated	(108)
	Exosomes	HPLC	Mesenchymal stem cells	—	Mice models of myocardial I/R injury	Reduce local and systemic inflammation	Restore bioenergetics Reduce oxidative stress Activate pro-survival signaling	(116)
	Endothelial MVs	Centrifugation 20,000 g	HCAECs	Monocytes	ApoE-deficient mice	Promote anti-inflammatory effects	Reduce endothelial ICAM-1 expression via the transfer of functional miRNA-222	(118)
	Endothelial exosomes	Centrifugation 20,500 g	KLF2-transduced or shear-stress-stimulated HUVECs	HASMCs	Aorta of ApoE knockout mice	Atheroprotection	EV-mediated transfer of miRNA-143/145	(120)
	Circulating MVs	Ultracentrifugation	Blood	VSMCs	ApoE-deficient mice	Penetrate the vascular wall Inhibit VSMCs proliferation and migration	miRNA-223-mediated IGF-1R/PI3K-Akt pathway	(121)

ApoE = apolipoprotein E; CMPC = cardiomyocyte progenitor cell; EC = endothelial cell; EMMPRIN = extracellular matrix metalloproteinase inducer; EMV = endothelial MV; HASMC = human aortic smooth muscle cell; HCAECs = human coronary artery endothelial cells; HMEC = human microvascular endothelial cell; HPLC = high-performance liquid chromatography; HUVEC = human umbilical vein endothelial cell; I/R = ischemia/reperfusion; ICAM = intercellular adhesion molecule; KLF = Krüppel-like factor; MI = myocardial infarction; MV = microvesicles; NO = nitric oxide; PMNs = polymorphonuclear leukocytes; RGS16 = regulator of G-protein signaling; RMVEC = rat renal microvascular endothelial cell; SPRED = sprouty-related EVH1 domain-containing protein; TNF = tumor necrosis factor; VSMC = vascular smooth muscle cell.