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Author Notes:

Correspondence and requests for materials should be addressed to M.E.D. (michael.davis@bme.emory.edu)

R.S.K. performed all delivery studies, imaging studies, and analyzed functional data.

J.C.S. and M.D. synthesized Hoechst-conjugates and performed some delivery studies.

MEB performed all animal surgeries, echocardiography, and invasive hemodynamics.

M.D.M. and E.B.C. assisted in delivery and imaging studies.

P.C. and K.D.P. helped with experimental design and in vitro characterization.

R.S.K., M.E.D. and N.M. wrote the manuscript, while J.C.S., R.S.K., M.E.D. and N.M. edited the manuscript.

Subjects:

Research Funding:

These publications have been funded in whole or in part with the Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN268201000043C to MED and NM, as well as a predoctoral fellowship from the American Heart Association to MDM (13PRE16980068).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • MULTIDISCIPLINARY SCIENCES
  • GROWTH-FACTOR-I
  • MYOCARDIAL-INFARCTION
  • MYOCYTE DEATH
  • ANGIOGENESIS
  • DYSFUNCTION
  • EXPRESSION
  • FAILURE
  • CELLS

Targeting Extracellular DNA to Deliver IGF-1 to the Injured Heart

Tools:

Journal Title:

Scientific Reports

Volume:

Volume 4

Publisher:

, Pages 4257-4257

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2014, Macmillan Publishers Limited. All rights reserved

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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