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Targeting extracellular DNA to deliver IGF-1 to the injured heart.
Khan, Raffay S; Martinez, Mario D; Sy, Jay C; Pendergrass, Karl D; Che, Pao-lin; Brown, Milton E; Cabigas, E Bernadette; Dasari, Madhuri; Murthy, Niren; Davis, Michael E.
Afiliação
  • Khan RS; Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
  • Martinez MD; Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia 30322, USA.
  • Sy JC; Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia 30322, USA.
  • Pendergrass KD; Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
  • Che PL; Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia 30322, USA.
  • Brown ME; 1] Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA [2] Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia 30322, USA.
  • Cabigas EB; Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia 30322, USA.
  • Dasari M; Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia 30322, USA.
  • Murthy N; 1] Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia 30322, USA [2] Department of Bioengineering, University of California at Berkeley, Berkeley, CA, 94720, USA.
  • Davis ME; 1] Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA [2] Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia 30322, USA [3] Department of Bioengineering, University of California at Berkeley, Berkeley, CA
Sci Rep ; 4: 4257, 2014 Mar 07.
Article em En | MEDLINE | ID: mdl-24604065
ABSTRACT
There is a great need for the development of therapeutic strategies that can target biomolecules to damaged myocardium. Necrosis of myocardium during a myocardial infarction (MI) is characterized by extracellular release of DNA, which can serve as a potential target for ischemic tissue. Hoechst, a histological stain that binds to double-stranded DNA can be conjugated to a variety of molecules. Insulin-like growth factor-1 (IGF-1), a small protein/polypeptide with a short circulating-half life is cardioprotective following MI but its clinical use is limited by poor delivery, as intra-myocardial injections have poor retention and chronic systemic presence has adverse side effects. Here, we present a novel delivery vehicle for IGF-1, via its conjugation to Hoechst for targeting infarcted tissue. Using a mouse model of ischemia-reperfusion, we demonstrate that intravenous delivery of Hoechst-IGF-1 results in activation of Akt, a downstream target of IGF-1 and protects from cardiac fibrosis and dysfunction following MI.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Fator de Crescimento Insulin-Like I / Infarto do Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Fator de Crescimento Insulin-Like I / Infarto do Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2014 Tipo de documento: Article