Table 6.

Molecular Mechanism of hucMSCs-EVs in Treating Different Diseases in the Circulatory System

HucMSCs-EVs Cargo	Target/Signaling	Conditions/ Diseases	Actiona	Reference
let-7a-5p	SMAD2	Viral myocarditis	Ferroptosis↓	[49]
None reported	AMPK/mTOR	Viral myocarditis	Apoptosis↓, cardiac function↑	[252]
miR-423-5p	EFNA3	MI	Angiogenesis↑	[253]
miR-23a-3p	DMT1	MI	Ferroptosis↓	[254]
MIF	miR-133a-3p/AKT	MI	Angiogenesis↑, apoptosis↓	[255]
miR-100-5p	NOX4	Heart failure	Oxidative stress↓, apoptosis↓	[256]
None reported	PI3K/Akt	Hypoxia/reoxygenation injury	Apoptosis↓	[257]
PINK1	PKA/NCLX	Myocardial injury	Protect mitochondria	[258]
miR-29b	None reported	MI	Fibrosis↓	[259]
miR-125b-5p	Smad7	MI	Fibrosis↓	[260]
lncRNA MALAT1	NF-κB/TNF-α	Aging-induced cardiac dysfunction	Inflammation↓	[261]
None reported	p38/JNK MAPK	Atherosclerosis	Inflammation↓	[262]
None reported	None reported	MI	Inflammation↓, apoptosis↓	[263]
miR-136	Apaf1	MI	The vitality of aged stem cells↑	[265]
None reported	PI3K/Akt	Heart transplantation	Myocardial ischemia-reperfusion injury↓	[266]
None reported	Wnt5a	PH	Right ventricular hypertrophy↓, pulmonary vascular remodeling↓, apoptosis↓, vascular stiffening↓	[268,269]
miR-147	None reported	AAA	Inflammation↓, vascular integrity↑, aneurysm progression↓	[270]
miR-126-3p	SPRED-1, PIK3R2, AKT/ERK1/2	Vein graft	Reendothelialization↑, neointimal hyperplasia↓	[271,272]
miR-148a-3p	Serpine1	Carotid artery ligation	Neointimal hyperplasia↓	[273]
miR-146a-5p	USP6	CML	Apoptosis↑	[274]
None reported	caspase-3, caspase-9	Leukemia	Sensitivity to chemotherapy drugs↑	[275]

Notes: ^a ↑ indicates promotion or upregulation; ↓ indicates inhibition or downregulation.