Author + information
- Received April 2, 2018
- Revision received December 27, 2018
- Accepted December 27, 2018
- Published online June 24, 2019.
- Shin Yajima, MD, PhDa,
- Shigeru Miyagawa, MD, PhDa,
- Satsuki Fukushima, MD, PhDa,
- Yoshiki Sakai, BSca,
- Hiroko Iseoka, PhDa,
- Akima Harada, BSca,
- Kayako Isohashi, MD, PhDb,
- Genki Horitsugi, BScb,
- Yuki Mori, PhDc,
- Motoko Shiozaki, PhDa,
- Hirotatsu Ohkawara, PhDa,
- Ryoto Sakaniwa, PhDd,
- Jun Hatazawa, MD, PhDb,
- Yoshichika Yoshioka, PhDc and
- Yoshiki Sawa, MD, PhDa,∗ ()
- aDepartment of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
- bDepartment of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka, Japan
- cDepartment of Biofunctional Imaging Laboratory, Immunology Frontier Research Center, Osaka University Graduate School of Medicine, Osaka, Japan
- dDepartment of Public Health, Osaka University Graduate School of Medicine, Osaka, Japan
- ↵∗Address for correspondence:
Dr. Yoshiki Sawa, Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
• 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.
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.
This work was supported by Grants-in-Aid for Scientific Research (KAKENHI), Tokyo, Japan (T16K106280). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors' institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received April 2, 2018.
- Revision received December 27, 2018.
- Accepted December 27, 2018.
- 2019 The Authors