Mitochondrial Metabolism and EV Cargo of Endothelial Cells Is Affected in Presence of EVs Derived from MSCs on Which HIF Is Activated

Abstract

Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) have attracted growing interest as a possible novel therapeutic agent for the management of different cardiovascular diseases (CVDs). Hypoxia significantly enhances the secretion of angiogenic mediators from MSCs as well as sEVs. The iron-chelating deferoxamine mesylate (DFO) is a stabilizer of hypoxia-inducible factor 1 and consequently used as a substitute for environmental hypoxia. The improved regenerative potential of DFO-treated MSCs has been attributed to the increased release of angiogenic factors, but whether this effect is also mediated by the secreted sEVs has not yet been investigated. In this study, we treated adipose-derived stem cells (ASCs) with a nontoxic dose of DFO to harvest sEVs (DFO-sEVs). Human umbilical vein endothelial cells (HUVECs) treated with DFO-sEVs underwent mRNA sequencing and miRNA profiling of sEV cargo (HUVEC-sEVs). The transcriptomes revealed the upregulation of mitochondrial genes linked to oxidative phosphorylation. Functional enrichment analysis on miRNAs of HUVEC-sEVs showed a connection with the signaling pathways of cell proliferation and angiogenesis. In conclusion, mesenchymal cells treated with DFO release sEVs that induce in the recipient endothelial cells molecular pathways and biological processes strongly linked to proliferation and angiogenesis.

Novel Perspective on Mechanism in Muscle Growth Inhibited by Ochratoxin A Associated with Ferroptosis: Model of Juvenile Grass Carp (Ctenopharyngodon idella) In Vivo and In Vitro Trials

“…Research has shown that at appropriate concentrations and action times, DFO could actively affect multiple stages of peripheral nerve regeneration in Schwann cells, thereby improving the effectiveness of nerve injury repair . Mesenchymal cells treated with low concentrations of DFO induce molecular pathways and biological processes closely related to proliferation and angiogenesis in recipient endothelial cells . This indicated that the different effects of DFO in different cells are closely related to its dosage and time of action and the research purpose.…”

“…64 Mesenchymal cells treated with low concentrations of DFO induce molecular pathways and biological processes closely related to proliferation and angiogenesis in recipient endothelial cells. 65 This indicated that the different effects of DFO in different cells are closely related to its dosage and time of action and the research purpose. Further research is needed to determine whether DFO alleviates OTA-inhibited cell proliferation in myoblasts.…”

Adipose-derived stem cell exosomes act as delivery vehicles of microRNAs in a dog model of chronic hepatitis

“…Exosomes act as messengers in the process of intercellular communication at a paracrine and endocrine level 5 , interacting with cells (as established in Figure 4 ) and transferring their cargo to recipient cells - thus changing their phenotype or regulating gene expression 14 . The exosome loading is sorted by ESCRT-dependent and independent mechanisms, and it is influenced by the parental cell and environmental characteristics 14 , 38 , 39 .…”

“…Exosomes play a major role in cell-cell communication both at a paracrine and systemic level. They are involved in either physiological processes (i.e., immune response, cell proliferation, and differentiation) or pathological ones (i.e., cancer progression, cardiovascular diseases) 1 , 4 , 5 . Exosomes contain nucleic acids, proteins, lipids, and other metabolites that are secreted by donor cells and taken up by recipient cells.…”

Molecular Research on Heart Protection

“…Zanotti et al explored the effects of sEVs released from DFO-treated ASCs (DFO-sEVs) on human umbilical vein endothelial cells (HUVECs). The authors used transcriptome sequencing and miRNA profiling of the sEV cargo (sEV-miRNA) of treated HUVECs and found significant enhancement of mitochondrial oxidative phosphorylation [ 9 ].…”