Prostacyclin Analogue–Loaded Nanoparticles Attenuate Myocardial Ischemia/Reperfusion Injury in Rats
| Autor: | Genki Horitsugi, Ryoto Sakaniwa, Hirotatsu Ohkawara, Jun Hatazawa, Shigeru Miyagawa, Yuki Mori, Yoshiki Sawa, Motoko Shiozaki, Kayako Isohashi, Shin Yajima, Satsuki Fukushima, Hiroko Iseoka, Yoshiki Sakai, Yoshichika Yoshioka, Akima Harada |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty lcsh:Diseases of the circulatory (Cardiovascular) system Myocardial ischemia Ischemia I/R ischemia/reperfusion MBF myocardial blood flow Prostacyclin 030204 cardiovascular system & hematology ischemia/reperfusion injury PET positron emission tomography Proinflammatory cytokine PRECLINICAL RESEARCH 03 medical and health sciences 0302 clinical medicine NP nanoparticle Internal medicine medicine EPR enhanced permeability and retention Myocardial tissue prostacyclin business.industry Blood flow medicine.disease Infarct size VEGF vascular endothelial growth factor ANG angiopoietin IL interleukin 030104 developmental biology lcsh:RC666-701 Cardiology nanoparticles Cardiology and Cardiovascular Medicine business ONO-1301 MRI magnetic resonance imaging Reperfusion injury PMNL polymorphonuclear leukocyte medicine.drug |
| Zdroj: | JACC: Basic to Translational Science, Vol 4, Iss 3, Pp 318-331 (2019) JACC: Basic to Translational Science |
| Popis: | Visual Abstract Highlights • Intravenously injected ONO-1301–containing nanoparticles selectively accumulated in the ischemic border area of the myocardium. • Prominent up-regulation occurred of proangiogenic cytokines such as vascular endothelial growth factor and angiopoietin-1 in the ischemic myocardium, which may have contributed to the preservation of the native vascular and capillary networks, thus preserving regional myocardial blood flow. • Down-regulation of the proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in the ischemic myocardium might have led to the attenuation of myocyte swelling and the suppression of the endothelial bleb formation, also contributing to the preservation of myocardial blood flow or the reduced infarct size. Summary Intravenously injected ONO-1301–containing nanoparticles (ONO-1301NPs), unlike an ONO-1301 solution, selectively accumulated in the ischemia/reperfusion (I/R)-injured myocardium of rats and contributed to the prolonged retention of ONO-1301 in the targeted myocardial tissue. In the ischemic area, proangiogenic cytokines were up-regulated and inflammatory cytokines were down-regulated upon ONO-1301NP administration. Consequently, ONO-1301NP–injected rats exhibited a smaller infarct size, better-preserved capillary networks, and a better-preserved myocardial blood flow at 24 h after I/R injury, compared with those in vehicle-injected or ONO-1301 solution–injected rats. ONO-1301NPs attenuate the myocardial I/R injury via proangiogenic and anti-inflammatory effects of the drug. |
| Databáze: | OpenAIRE |
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