Abstract | AIM: There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction (AMI), for which the effectiveness of interventional reperfusion therapy is hampered by myocardial ischemia-reperfusion (IR) injury. Pretreatment with statins before ischemia is shown to reduce MI size in animals. However, no benefit was found in animals and patients with AMI when administered at the time of reperfusion, suggesting insufficient drug targeting into the IR myocardium. Here we tested the hypothesis that nanoparticle-mediated targeting of pitavastatin protects the heart from IR injury. METHODS AND RESULTS: CONCLUSIONS: Nanoparticle-mediated targeting of pitavastatin induced cardioprotection from IR injury by activation of PI3K/Akt pathway and inhibition of inflammation and cardiomyocyte death in this model. This strategy can be developed as an innovative cardioprotective modality that may advance currently unsatisfactory reperfusion therapy for AMI.
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Authors | Kazuhiro Nagaoka, Tetsuya Matoba, Yajing Mao, Yasuhiro Nakano, Gentaro Ikeda, Shizuka Egusa, Masaki Tokutome, Ryoji Nagahama, Kaku Nakano, Kenji Sunagawa, Kensuke Egashira |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 7
Pg. e0132451
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 26167913
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cardiotonic Agents
- Quinolines
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- pitavastatin
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Topics |
- Animals
- Blotting, Western
- Capillary Permeability
- Cardiotonic Agents
(administration & dosage, analysis, blood, therapeutic use)
- Disease Models, Animal
- Drug Delivery Systems
(methods)
- Echocardiography
- Flow Cytometry
- Injections, Intravenous
- Male
- Myocardial Infarction
(drug therapy)
- Myocardial Reperfusion Injury
(prevention & control)
- Myocardium
(chemistry, pathology)
- Nanoparticles
(therapeutic use)
- Phosphatidylinositol 3-Kinases
(physiology)
- Proto-Oncogene Proteins c-akt
(physiology)
- Quinolines
(administration & dosage, analysis, blood, therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Signal Transduction
(drug effects)
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