Iovascular Investigation Center, Icahn College of Medicine at Mount Sinai, New York, USA; 2Feinberg Cardiovascular

Iovascular Investigation Center, Icahn College of Medicine at Mount Sinai, New York, USA; 2Feinberg Cardiovascular Analysis Institute, Feinberg College of Medicine, Northwestern University, IL, USA; 3Caladrius Biosciences, NY, USAOF14.Endothelial cell-derived extracellular vesicles in acute myocardial infarction Naveed Akbar1, Janet Digby1, Thomas Cahill1, Abhijeet Tavare1, Sushant Saluja1, Sam Dawkins1, Laurienne Edgar1, Nadia Rawlings1, Klemen Ziberna1, Eileen McNeil1, Errin Johnson1, Alaa Aljabali1, Rebecca Dragovic1, Mala Rohling1, Grant Belgard2, David Greaves1, Keith Channon1, Daniel Anthony1 and Robin ChoudhuryUniversity of Oxford, Oxford, Uk; 2Verge GenomicsBackground: The mechanism by which acute myocardial infarction (AMI) mobilises monocytes from the spleen into peripheral blood and induces transcriptional activation remains unknown. Right here we report thePrevious studies in our lab have found that therapeutically vital human CD34+ hematopoietic stem cells secrete exosomes (Exo) to induce angiogenic activity each in vitro and in vivo. MicroRNA microarray evaluation suggests that CD34+ exosomes (CD34Exo) carry MMP-10 MedChemExpress proangiogenic miRNAs, like miR-126, which have an effect on the therapeutic function of CD34Exo. Here, we hypothesise that hypoxic treatment of CD34+ stem cells can modulate the miRNA content material and regenerative efficacy of CD34Exo. Exosomes from human CD34+ cells cultured Caspase 1 list beneath hypoxia (H-Exo) were additional proliferative, anti-apoptotic and angiogenic in vitro, when compared with exosomes from cells under normoxia (N-Exo). In a mouse model of hind limb ischemia (BalbC nude), H-Exo remedy drastically enhanced limb perfusion, improved capillary density, and prevented ischemic limb amputation in comparison to N-Exo. To recognize the aspects responsible for enhanced therapeutic function of H-Exo, we compared each protein and miRNA elements of H- and N-Exo. Employing 2D-DIGE and mass spectrometry evaluation, we found that expression of big proteins in H-Exo didn’t differ drastically than N-Exo. However, expression of proangiogenic miRNAs was increased substantially in H-Exo (e.g. miR-210 and miR-126) when compared with N-Exo. We’ve examined the role of ETS-1, a transcription factor induced by hypoxia-inducible fator-1 (HIF-1), in regulating the expression of miR126. We propose that HIF-1/ETS-1 regulatory mechanisms impact the expression of exosomal miR-126 beneath hypoxia. These results are becoming confirmed utilizing siRNA silencing and making use of HIF hydroxylase inhibitor dimethyloxalylglycine. We conclude that hypoxia-induced miR-126 expression in CD34 cellderived exosomes stimulating exosomes-mediated angiogenesis and therapeutic recovery by means of ETS-transcriptional pathway. Our perform has essential clinical implications to improve therapeutic angiogenesis, in particular in diabetic and cardiovascular individuals, who’ve stem cells with diminished angiogenic possible.Friday, Could 19,OF14.Circulating exosomes correlate with metabolic syndrome severity and evoke changes of mitochondrial dynamic which are associated with endothelial dysfunction Marine Malloci1, Madlyne Esnault2, Zainab Safiedeen2, Severine Dubois3, Jerome Boursier4, Frederic Gagnadoux4, Ramaroson Andriantsitohaina1, Gilles Simard3 and M. Carmen MartinezINSERM U1063; 2INSERM UMR1063 University of Angers, France; INSERM U1063/Angers University Hospital, Angers, France; 4CHU d’Angers, Angers, FranceMetabolic syndrome (MetS) is characterised by a cluster of interrelated risk elements -hyperglycemia, dy.