<b>Exosomal miR‐1-3p regulates human umbilical vein endothelial cell</b><b>s</b><b> proliferation and apoptosis by targeting VEGFα in a heat stroke model</b>

<b>Abstract</b><b>Objective:</b><b> </b>Accumulating evidence demonstrates that exosomal microRNAs (miRNAs) play pivotal roles in multiple diseases, but little is known about their impacts on multi-organ failure in heat stroke. This study aimed to determine the functions of exosomal microRNAs in the development of heat stroke.<b>Methods:</b> Human umbilical vein endothelial cell (HUVEC)-derived exosomes were collected after heat stress and assessed by microRNA sequencing. Differentially expressed exosome-encapsulated miRNAs were verified in exosome-enriched serum samples by qRT-PCR. Bioinformatics was used to identify the miRNA targets. HUVEC-derived exosomes after heat stress were administered to mice. Thrombotic factors were assessed in the mouse models and serum from heat stroke patients.<b>Results:</b> In this study, miR-1-3p was significantly upregulated after heat stress. Heat-treated HUVEC exosomes impaired HUVEC proliferation, viability, and migration, while enhancing apoptosis; the inhibition of exosomal miR-1-3p expression partially alleviated the above effects. We found that exosomal miR-1-3p in 41°C heat stress-treated HUVECs could remarkably increase the amounts of tissue factor (TF), von Willebrand factor (vWF), and PAI-1 (plasminogen activator inhibitor-1), and similar trends of changes were also seen in vivo experiments. Bioinformatics suggested VEGFα as a potential miR-1-3p target, which was verified by a dual-luciferase assay. miR-1-3p blockade induced VEGFα expression, while its upregulation suppressed VEGFα. Ectopic expression of VEGFα partially suppressed the impairing effects of heat-treated exosomes. In mice and humans, exosomal miR-1-3p seemed to regulate angiogenesis by targeting VEGFα.<b>Conclusion:</b><b> </b>In a heat stroke model, exosomal miR-1-3p regulated HUVEC proliferation, viability, migration, and apoptosis by targeting VEGFα. Exosomal miR-1-3p may contribute to the diagnosis/treatment of heat stroke.