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MicroRNA-126 (miR-126) is reported to regulate angiogenesis by blocking Sprouty-related EVH1 domain-containing protein 1 (SPRED1), an endogenous inhibitor of vascular endothelial cell growth factor. In this study, we investigated the angiogenic effects of the sustained release of miR-126 loaded with poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) in a murine hindlimb ischemia model.We induced mice hindlimb ischemia through femoral artery excision. We randomly assigned the mice to two groups and performed an intramuscular injection of miR-126-loaded PLGA NPs (miR-126) or scrambled miR-loaded PLGA NPs (control) shortly after induction of ischemia.The miR-126 expression levels in the ischemic limb at 3 days after treatment were significantly higher in mice treated with miR-126-loaded PLGA NPs than in those with scrambled miR, indicating the fair efficiency of local miR transduction (control vs miR-126: 0.33 ± 0.12 vs 0.74 ± 0.42; P .05; n = 6). Laser Doppler perfusion imaging revealed that limb blood flow in mice treated with miR-126-loaded PLGA NPs was significantly higher at 14 days after treatment (sham vs control vs miR-126: 0.62 ± 0.09 vs 0.58 ± 0.05 vs 0.72 ± 0.07; P .001; n = 12). Immunohistochemical analysis indicated that CD31-positive cell density and α-smooth muscle actin-positive vessel density were significantly higher in miR-126-treated mice (control vs miR-126: 0.33 ± 0.12 vs 0.74 ± 0.42; P .05; n = 6). SPRED1 messenger RNA expression levels were significantly lower in miR-126-treated mice (control vs miR-126: 1.00 ± 0.05 vs 0.81 ± 0.07; P .05; n = 6). Western blotting indicated that protein levels of pERK/ERK mediated by SPRED1 were significantly higher in miR-126-treated mice (control vs miR-126: 0.29 ± 0.10 vs 0.54 ± 0.21; P .05; n = 6).This study suggests that sustained release of miR-126-loaded PLGA NPs might be an effective method in therapeutic angiogenesis for hindlimb ischemia."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420001326207122432","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"20325781"},{"@type":"NRID","@value":"1000020325781"},{"@type":"NRID","@value":"9000001152854"},{"@type":"NRID","@value":"9000004294619"},{"@type":"NRID","@value":"9000256911703"},{"@type":"NRID","@value":"9000002871761"},{"@type":"NRID","@value":"9000002891349"},{"@type":"NRID","@value":"9000003451589"},{"@type":"NRID","@value":"9000021697402"},{"@type":"NRID","@value":"9000253439246"},{"@type":"NRID","@value":"9000255947224"},{"@type":"NRID","@value":"9000006122066"},{"@type":"NRID","@value":"9000005800074"},{"@type":"NRID","@value":"9000016834290"},{"@type":"NRID","@value":"9000253437932"},{"@type":"NRID","@value":"9000256849382"},{"@type":"NRID","@value":"9000242694440"},{"@type":"NRID","@value":"9000004051237"},{"@type":"NRID","@value":"9000017339431"},{"@type":"NRID","@value":"9000238323653"},{"@type":"NRID","@value":"9000345258976"},{"@type":"NRID","@value":"9000253444079"},{"@type":"NRID","@value":"9000283454492"},{"@type":"NRID","@value":"9000314072579"},{"@type":"NRID","@value":"9000001613286"},{"@type":"NRID","@value":"9000002892784"},{"@type":"NRID","@value":"9000003910531"},{"@type":"NRID","@value":"9000362235875"},{"@type":"NRID","@value":"9000252868397"},{"@type":"NRID","@value":"9000252869134"},{"@type":"NRID","@value":"9000252874144"},{"@type":"NRID","@value":"9000256632179"},{"@type":"NRID","@value":"9000017394428"},{"@type":"NRID","@value":"9000242794267"},{"@type":"NRID","@value":"9000319050597"},{"@type":"NRID","@value":"9000316691105"},{"@type":"NRID","@value":"9000253221472"},{"@type":"NRID","@value":"9000253457486"},{"@type":"NRID","@value":"9000004015839"},{"@type":"NRID","@value":"9000314804391"},{"@type":"NRID","@value":"9000243902831"},{"@type":"NRID","@value":"9000253448663"},{"@type":"NRID","@value":"9000253446602"},{"@type":"NRID","@value":"9000258235125"},{"@type":"NRID","@value":"9000258234160"},{"@type":"NRID","@value":"9000258234391"},{"@type":"NRID","@value":"9000017303418"},{"@type":"NRID","@value":"9000258743152"},{"@type":"NRID","@value":"9000003903299"},{"@type":"NRID","@value":"9000317164749"},{"@type":"NRID","@value":"9000243877791"},{"@type":"NRID","@value":"9000253455992"},{"@type":"NRID","@value":"9000253461215"},{"@type":"NRID","@value":"9000253444653"},{"@type":"NRID","@value":"9000014685921"},{"@type":"NRID","@value":"9000018191608"},{"@type":"NRID","@value":"9000023334069"},{"@type":"NRID","@value":"9000254509484"},{"@type":"NRID","@value":"9000254374897"},{"@type":"NRID","@value":"9000252871528"},{"@type":"NRID","@value":"9000257918639"},{"@type":"NRID","@value":"9000017949263"},{"@type":"NRID","@value":"9000262372344"},{"@type":"NRID","@value":"9000240539036"},{"@type":"NRID","@value":"9000020273566"},{"@type":"NRID","@value":"9000253448119"},{"@type":"NRID","@value":"9000254097694"},{"@type":"NRID","@value":"9000258235170"},{"@type":"NRID","@value":"9000000991896"},{"@type":"NRID","@value":"9000002152367"},{"@type":"NRID","@value":"9000238243997"},{"@type":"NRID","@value":"9000253451398"},{"@type":"NRID","@value":"9000258000846"},{"@type":"NRID","@value":"9000283704098"},{"@type":"NRID","@value":"9000258235241"},{"@type":"NRID","@value":"9000256846070"},{"@type":"NRID","@value":"9000256630384"},{"@type":"NRID","@value":"9000024140401"},{"@type":"NRID","@value":"9000255953677"},{"@type":"NRID","@value":"9000243753501"},{"@type":"NRID","@value":"9000345307415"},{"@type":"NRID","@value":"9000350558230"},{"@type":"NRID","@value":"9000253438341"},{"@type":"NRID","@value":"9000256877769"},{"@type":"NRID","@value":"9000022220113"},{"@type":"NRID","@value":"9000264550380"},{"@type":"NRID","@value":"9000252870090"},{"@type":"NRID","@value":"9000252870720"},{"@type":"NRID","@value":"9000024678924"},{"@type":"NRID","@value":"9000021746682"},{"@type":"NRID","@value":"9000256633609"},{"@type":"NRID","@value":"9000256639081"},{"@type":"NRID","@value":"9000015166360"},{"@type":"NRID","@value":"9000248230075"},{"@type":"NRID","@value":"9000253454671"},{"@type":"NRID","@value":"9000253445586"},{"@type":"NRID","@value":"9000254896170"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0103347"}],"foaf:name":[{"@value":"Ryuzo 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Acid Copolymer"},{"@id":"https://cir.nii.ac.jp/all?q=Ischemia","dc:title":"Ischemia"},{"@id":"https://cir.nii.ac.jp/all?q=Regional%20Blood%20Flow","dc:title":"Regional Blood Flow"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Nanoparticles","dc:title":"Nanoparticles"},{"@id":"https://cir.nii.ac.jp/all?q=Phosphorylation","dc:title":"Phosphorylation"},{"@id":"https://cir.nii.ac.jp/all?q=Extracellular%20Signal-Regulated%20MAP%20Kinases","dc:title":"Extracellular Signal-Regulated MAP Kinases"},{"@id":"https://cir.nii.ac.jp/all?q=Muscle,%20Skeletal","dc:title":"Muscle, Skeletal"},{"@id":"https://cir.nii.ac.jp/all?q=Blood%20Flow%20Velocity","dc:title":"Blood Flow Velocity"},{"@id":"https://cir.nii.ac.jp/all?q=Adaptor%20Proteins,%20Signal%20Transducing","dc:title":"Adaptor Proteins, Signal Transducing"},{"@id":"https://cir.nii.ac.jp/all?q=Signal%20Transduction","dc:title":"Signal 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