Advances in Exosomes Derived from Different Cell Sources and Cardiovascular Diseases

Table 1

Summary of exosomes derived from different cell sources in cardiovascular diseases.

Source	Cargos	Biological effects	Evidences	References
Cardiomyocytes	HSP20	Promote angiogenesis by activating VEGFR2, and activate AKT signaling pathway and repress TNF-α and IL-1β factors to alleviate myocardial infarction	Preclinical evidences (in vivo and in vitro)	[20, 21]
	HSP60	Promote immune responses	Preclinical evidences (in vitro)	[23]
	HSP70	Activate monocytes alone, resulting in monocyte adhesion to endothelial cells; improve cardiac function	Preclinical evidences (in vitro)	[16, 17]
	HSP90 and IL-6	Active STAT-3 signaling in cardiac fibroblasts that culminates in excess collagen synthesis, leading to severely compromised cardiac function during cardiac hypertrophy	Preclinical evidences (in vivo and in vitro)	[24]
	TNF-α	Interact with HIF-1α to contribute to cardiac remodeling	Preclinical evidences (in vitro)	[25]
	GLUT	Increase glucose transport	Preclinical evidences (in vitro)	[26]
	miR-15b, miR-17, miR-20a, miR-103, miR-199a, miR-210, and miR-292	Enhance angiogenesis, reduce profibrotic gene expression, preserve myocardial contractile function, and improve cardiac function	Preclinical evidences (in vivo and in vitro)	[90]
	miR-29b, miR-323-5p, miR-455, and miR-466	Mediate the regulation of MMP9, which is involved in matrix degradation and leads to fibrosis and myocyte uncoupling	Preclinical evidences (in vitro)	[31]
	miR-30a	Regulate autophagy by affecting the expression of Beclin-1, ATG12, and the ratio of LC3II/LC3I	Preclinical evidences (in vitro)	[30]
	miR-34a	Biomarkers of myocardial infarction	Preclinical evidences (in vitro)	[14]
	miR-146a	Inhibit apoptosis and promote proliferation of cardiomyocytes, while enhancing angiogenesis	Preclinical evidences (in vivo and in vitro)	[27]
	miR-208a	Increase fibroblast proliferation and differentiation into myofibroblasts via targeting Dyrk2	Preclinical evidences (in vivo and in vitro)	[32]
	miR-320	Inhibit proliferation, migration, and tube-like formation	Preclinical evidences (in vivo and in vitro)	[29]
	miR-451	Protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation and inhibit cardiomyocyte apoptosis	Preclinical evidences (in vivo and in vitro)	[39]
	NA	Reduce apoptosis and fibrosis	Preclinical evidences (in vivo and in vitro)	[28]
	NA	Activate fibroblasts, which can increase the secretion of angiogenic factor, SDF1 and VEGF by fibroblasts	Preclinical evidences (in vivo and in vitro)	[33, 34]
	NA	Promote angiogenesis and cardiac protection	Preclinical evidences (in vivo and in vitro)	[34]
Cardiac progenitor cells	PAPP-A	Cardioprotection profile through releasing IGF-1 via proteolytic cleavage of IGFBP-4, resulting in IGF-1R activation, intracellular Akt and ERK1/2 phosphorylation	Preclinical evidences (in vivo and in vitro)	[87]
	miR-15b and miR-20a	Stimulate angiogenesis	Preclinical evidences (in vivo and in vitro)	[38]
	miR-17 and miR-103	Promote angiogenesis, inhibit myocardial fibrosis	Preclinical evidences (in vivo and in vitro)	[38]
	miR-21	Inhibit cardiomyocyte apoptosis through downregulating PDCD4; downregulate both infarction size and injury marker expressions in vivo and promote endothelial cell proliferation, inhibit the apoptosis, and stimulate angiogenesis in vitro by targeting PTEN	Preclinical evidences (in vivo and in vitro)	[41, 42]
	miR-126 and; miR-210	Active kinase and induce glycolysis	Preclinical evidences (in vivo and in vitro)	[40]
	miR-132, miR-210, and miR-146a-3p	Decrease myocardial apoptosis, increase angiogenesis, and improve left ventricular ejection fraction	Preclinical evidences (in vivo and in vitro)	[27, 36, 37]
	miR-133a	Improve cardiac function by reducing fibrosis and hypertrophy and increasing vascularization and cardiomyocyte proliferation	Preclinical evidences (in vivo and in vitro)	[44]
	miR-146a-5p	Attenuate doxorubicin/trastuzumab-induced oxidative stress in cardiomyocytes through suppressing target genes Traf6, Smad4, Irak1, Nox4, and Mpo	Clinical evidences	[43]
	miR-181a and miR-323-5p	Promote angiogenesis	Preclinical evidences (in vivo and in vitro)	[27, 36]
	miR-210	Promote angiogenesis, inhibit cardiomyocyte apoptosis, improve heart function	Preclinical evidences (in vivo and in vitro)	[38]
	lnc RNA MALAT1	Promote the infarct healing through improvement of cardiomyocyte survival and angiogenesis by targeting the miRNA	Preclinical evidences (in vivo and in vitro)	[45]
	NA	Stimulate cell migration	Preclinical evidences (in vitro)	[46]
Fibroblasts	miR-21-3p	Induce cardiomyocyte hypertrophy by targeting SORBS2 and PDLIM5	Preclinical evidences (in vivo and in vitro)	[47]
	miR-21, miR-29, and miR-30	Biomarkers of left ventricular hypertrophy	Preclinical evidences (in vivo and in vitro)	[48]
	miR-34a	Biomarkers of myocardial infarction	Preclinical evidences (in vitro)	[14]
Mesenchymal stem cells	NA	Reduce the infarct area, inhibit the proliferation and migration of vascular smooth muscle, reduce cardiomyocyte apoptosis, promote angiogenesis, reduce ventricular remodeling, and protect cardiac function	Preclinical evidences (in vivo and in vitro)	[52–55]
	NA	Protect cardiomyocytes from apoptosis through lncRNA-NEAT1/miR-142-3p/FOXO1 signaling pathway	Preclinical evidences (in vitro)	[56, 57]
	NA	Reduce the levels of inflammatory factors, such as IL-6 and MCP-1, through activating the signal pathways involved in IGF-1/PI3K/Akt and GSK-3p	Preclinical evidences (in vivo and in vitro)	[52–54, 58, 59]
	NA	Inhibit vascular remodeling and hypertension by inhibiting STAT3 signaling pathway	Preclinical evidences (in vivo and in vitro)	[60]
	NA	Reverse pulmonary hypertension	Preclinical evidences (in vivo)	[61]
	miR-126 and miR-130a	Biomarkers of chronic heart failure	Clinical evidences	[67]
	miR-294	Increase neovascularization, cardiomyocyte survival, and reduce fibrosis	Preclinical evidences (in vivo and in vitro)	[66]
Endothelial cells	KLF2	Attenuate the formation of atherosclerosis	Preclinical evidences (in vivo and in vitro)	[49]
	miR-10b-5p	Ameliorate cardiac fibroblast activation	Preclinical evidences (in vitro)	[89]
	miR-146a-5p and miR-146b-5p	Inhibit the migration and angiogenesis	Preclinical evidences (in vitro)	[88]
Macrophages and leukocyte	NA	Promote vascular smooth muscle cells migration and adhesion, which may be mediated by the integration of extracellular vesicles into vascular smooth muscle cells and the subsequent downstream activation of ERK and Akt	Preclinical evidences (in vitro)	[51]
		Biomarkers of atherosclerosis	Clinical evidences	[50]
Cardiac stromal cells	miR-21-5p	Contribute to heart repair by enhancing angiogenesis and cardiomyocyte survival through the phosphatase and tensin homolog/Akt pathway	Pre-clinical evidences (in vivo and in vitro)	[93]