1 Ocak 2019 Dergi makalesi Açık Erişim

Icli, Basak; Wu, Winona; Ozdemir, Denizhan; Li, Hao; Cheng, Henry S.; Haemmig, Stefan; Liu, Xin; Giatsidis, Giorgio; Avci, Seyma Nazli; Lee, Nathan; Guimaraes, Raphael Boesch; Manica, Andre; Marchini, Julio F.; Rynning, Stein Erik; Risnes, Ivar; Hollan, Ivana; Croce, Kevin; Yang, Xianbin; Orgill, Dennis P.; Feinberg, Mark W.

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    "creators": [
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 77 Ave Louis Pasteur,NRB 742F, Boston, MA 02115 USA", 
        "name": "Icli, Basak"
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 77 Ave Louis Pasteur,NRB 742F, Boston, MA 02115 USA", 
        "name": "Wu, Winona"
      }, 
      {
        "name": "Ozdemir, Denizhan"
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 77 Ave Louis Pasteur,NRB 742F, Boston, MA 02115 USA", 
        "name": "Li, Hao"
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 77 Ave Louis Pasteur,NRB 742F, Boston, MA 02115 USA", 
        "name": "Cheng, Henry S."
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 77 Ave Louis Pasteur,NRB 742F, Boston, MA 02115 USA", 
        "name": "Haemmig, Stefan"
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 77 Ave Louis Pasteur,NRB 742F, Boston, MA 02115 USA", 
        "name": "Liu, Xin"
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Div Plast Surg, Dept Surg, Boston, MA 02115 USA", 
        "name": "Giatsidis, Giorgio"
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 77 Ave Louis Pasteur,NRB 742F, Boston, MA 02115 USA", 
        "name": "Avci, Seyma Nazli"
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 77 Ave Louis Pasteur,NRB 742F, Boston, MA 02115 USA", 
        "name": "Lee, Nathan"
      }, 
      {
        "affiliation": "Fundacao Univ Cardiol ICFUC, Inst Cardiol Rio Grande Sul, Porto Alegre, RS, Brazil", 
        "name": "Guimaraes, Raphael Boesch"
      }, 
      {
        "affiliation": "Fundacao Univ Cardiol ICFUC, Inst Cardiol Rio Grande Sul, Porto Alegre, RS, Brazil", 
        "name": "Manica, Andre"
      }, 
      {
        "affiliation": "Univ Sao Paulo, Med Sch, Inst Heart, Sao Paulo, Brazil", 
        "name": "Marchini, Julio F."
      }, 
      {
        "affiliation": "LHL Hosp Gardermoen, Dept Cardiac Surg, Jessheim, Norway", 
        "name": "Rynning, Stein Erik"
      }, 
      {
        "affiliation": "LHL Hosp Gardermoen, Dept Cardiac Surg, Jessheim, Norway", 
        "name": "Risnes, Ivar"
      }, 
      {
        "affiliation": "Lillehammer Hosp Rheumat Dis, Dept Rheumatol, Lillehammer, Norway", 
        "name": "Hollan, Ivana"
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 77 Ave Louis Pasteur,NRB 742F, Boston, MA 02115 USA", 
        "name": "Croce, Kevin"
      }, 
      {
        "affiliation": "AM Biotechnol LLC, Houston, TX USA", 
        "name": "Yang, Xianbin"
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Div Plast Surg, Dept Surg, Boston, MA 02115 USA", 
        "name": "Orgill, Dennis P."
      }, 
      {
        "affiliation": "Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 77 Ave Louis Pasteur,NRB 742F, Boston, MA 02115 USA", 
        "name": "Feinberg, Mark W."
      }
    ], 
    "description": "Objective- In response to tissue injury, the appropriate progression of events in angiogenesis is controlled by a careful balance between pro and antiangiogenic factors. We aimed to identify and characterize microRNAs that regulate angiogenesis in response to tissue injury. Approach and Results- We show that in response to tissue injury, microRNA-615-5p (miR-615-5p) is rapidly induced and serves as an antiangiogenic microRNA by targeting endothelial cell VEGF (vascular endothelial growth factor)-AKT (protein kinase B)/eNOS (endothelial nitric oxide synthase) signaling in vitro and in vivo. MiR-615-5p expression is increased in wounds of diabetic db/db mice, in plasma of human subjects with acute coronary syndromes, and in plasma and skin of human subjects with diabetes mellitus. Ectopic expression of miR-615-5p markedly inhibited endothelial cell proliferation, migration, network tube formation in Matrigel, and the release of nitric oxide, whereas miR-615-5p neutralization had the opposite effects. Mechanistic studies using transcriptomic profiling, bioinformatics, 3 ' untranslated region reporter and microribonucleoprotein immunoprecipitation assays, and small interfering RNA dependency studies demonstrate that miR-615-5p inhibits the VEGF-AKT/eNOS signaling pathway in endothelial cells by targeting IGF2 (insulin-like growth factor 2) and RASSF2 (Ras-associating domain family member 2). Local delivery of miR-615-5p inhibitors, markedly increased angiogenesis, granulation tissue thickness, and wound closure rates in db/db mice, whereas miR-615-5p mimics impaired these effects. Systemic miR-615-5p neutralization improved skeletal muscle perfusion and angiogenesis after hindlimb ischemia in db/db mice. Finally, modulation of miR-615-5p expression dynamically regulated VEGF-induced AKT signaling and angiogenesis in human skin organoids as a model of tissue injury. Conclusions- These findings establish miR-615-5p as an inhibitor of VEGF-AKT/eNOS-mediated endothelial cell angiogenic responses and that manipulating miR-615-5p expression could provide a new target for angiogenic therapy in response to tissue injury.", 
    "doi": "10.1161/ATVBAHA.119.312726", 
    "has_grant": false, 
    "journal": {
      "issue": "7", 
      "pages": "1458-1474", 
      "title": "ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY", 
      "volume": "39"
    }, 
    "license": {
      "id": "cc-by"
    }, 
    "publication_date": "2019-01-01", 
    "relations": {
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    "resource_type": {
      "subtype": "article", 
      "title": "Dergi makalesi", 
      "type": "publication"
    }, 
    "title": "MicroRNA-615-5p Regulates Angiogenesis and Tissue Repair by Targeting AKT/eNOS (Protein Kinase B/Endothelial Nitric Oxide Synthase) Signaling in Endothelial Cells"
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  "revision": 1, 
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