Microvesicles‐mediated communication between endothelial cells modulates, endothelial survival, and angiogenic function via transferring of miR‐125a‐5p

Endothelial cells (ECs) released microvesicles (EMVs) could modulate the functions of target cells by transferring their microRNAs (miRs). We have reported that miR‐125a‐5p protected EC function. In this study, we determined whether EMVs provided beneficial effects on ECs by transferring miR‐125a‐5p. Human brain microvessel ECs were transfected with miR‐125a‐5p mimic or miR‐125a‐5p short hairpin RNA to obtain miR‐125a‐5p overexpressing ECs and miR‐125a‐5p knockdown ECs, and their derived EMVs. For the functional study, ECs or hypoxia/reoxygenation injured ECs were coincubated with various EMVs. The survival and angiogenic function of ECs were measured. Western blot and quantitative real time polymerase chain reaction (qRT‐PCR) were used for measuring the levels of phosphoinositide 3‐kinase (PI3K), phosphorylation‐Akt (p‐Akt)/Akt, p‐endothelial nitric oxide synthase (p‐eNOS), cleaved caspase‐3, and miR‐125a‐5p. PI3K inhibitor was used for pathway analysis. EMVs promoted the proliferation, migration, and tube formation ability of ECs, and alleviated the apoptotic rate of ECs. These effects were associated by an increase in p‐Akt/Akt and p‐eNOS, and a decrease in cleaved caspase‐3 could be abolished by LY294002. Overexpression or downregulation of miR‐125a‐5p in EMVs promoted or inhibited those effects of EMVs. EMVs could enhance the survival and angiogenic function of ECs via delivering miR‐125a‐5p to modulate the expression of PI3K/Akt/eNOS pathway and caspase‐3. We showed that endothelial cells (ECs) released microvesicles (EMVs) to promote survival and angiogenic function of normal and hypoxia/reoxygenation injured ECs. The underlying mechanisms were associated with the expressions of phosphoinositide 3‐kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) pathway and caspase‐3.