Targeting Extracellular DNA to Deliver IGF-1 to the Injured Heart
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 h...
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| Format: | Online |
| Language: | English |
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Nature Publishing Group
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945489/ |
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pubmed-3945489 |
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oai_dc |
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pubmed-39454892014-03-10 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. Article 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. Nature Publishing Group 2014-03-07 /pmc/articles/PMC3945489/ /pubmed/24604065 http://dx.doi.org/10.1038/srep04257 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
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. |
| spellingShingle |
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. Targeting Extracellular DNA to Deliver IGF-1 to the Injured Heart |
| author_facet |
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. |
| author_sort |
Khan, Raffay S. |
| title |
Targeting Extracellular DNA to Deliver IGF-1 to the Injured Heart |
| title_short |
Targeting Extracellular DNA to Deliver IGF-1 to the Injured Heart |
| title_full |
Targeting Extracellular DNA to Deliver IGF-1 to the Injured Heart |
| title_fullStr |
Targeting Extracellular DNA to Deliver IGF-1 to the Injured Heart |
| title_full_unstemmed |
Targeting Extracellular DNA to Deliver IGF-1 to the Injured Heart |
| title_sort |
targeting extracellular dna to deliver igf-1 to the injured heart |
| description |
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. |
| publisher |
Nature Publishing Group |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945489/ |
| _version_ |
1612065387160010752 |