1: MRP1-Dependent Extracellular Release of Glutathione Induces Cardiomyocyte Ferroptosis After Ischemia-Reperfusion

Circ Res.

2023 Oct 27;133(10):861-876. doi: 10.1161

Genki Ichihara, Yoshinori Katsumata, Yuki Sugiura, Yuta Matsuoka, Rae Maeda, Jin Endo, Atsushi Anzai, Kohsuke Shirakawa, Hidenori Moriyama, Hiroki Kitakata, Takahiro Hiraide, Shinichi Goto, Seien Ko, Yuji Iwasawa, Kazuhisa Sugai, Kyohei Daigo, Shinya Goto, Kazuki Sato, Ken-ichi Yamada, Makoto Suematsu, Masaki Ieda and Motoaki Sano

Myocardial infarction is a major cause of death for many people, and even with treatment (reperfusion therapy), the risk of myocardial necrosis and heart failure is known to be high. In particular, the generation of reactive oxygen species immediately after reperfusion has been considered a problem, but the development of therapeutic methods has been difficult. Conventional research methods involved collecting myocardial tissue after ischemia-reperfusion and measuring various metabolites and proteins to search for molecular targets for treatment. With this method, it was impossible to track the dynamic changes in the metabolic state of the myocardium over time. Therefore, we developed a method (microdialysis) in which a tubular semipermeable membrane is implanted into the heart wall to continuously collect and measure metabolites in the myocardial interstitium. This allowed us to successfully observe in detail the stepwise progression of ischemia-reperfusion injury in the myocardium of living disease model mice. We clarified that in cardiac ischemia-reperfusion injury, the accumulation of oxidized lipids and ferroptosis begin at a relatively late stage after ischemia-reperfusion (6 hours or more after reperfusion). The cause is the leakage of a powerful reducing substance called glutathione out of the cells, mainly via MRP1 (multidrug resistance protein 1), during ischemia-reperfusion. We also found that pharmacological inhibition of MRP1 reduces the size of the myocardial infarction area.

(Yoshinori Katsumata, 84th class, Institute for Integrated Sports Medicine / Department of Cardiology)

Radiology.

2023 Sep;308(3):e230743. doi: 10.1148

Takehiro Nakahara , Yu Iwabuchi, Raita Miyazawa, Kai Tonda, Tohru Shiga, H. William Strauss, Charalambos Antoniades, Jagat Narula, Masahiro Jinzaki

It is well known that myocarditis can occur after SARS-CoV-2 vaccination. 18F-fluorodeoxyglucose (FDG) is a PET agent that allows observation of glucose metabolism. While primarily used for tumor evaluation, it is also known to show accumulation in cases of myocarditis. Therefore, we investigated whether myocardial FDG uptake is generally elevated in asymptomatic patients after vaccination. We conducted a retrospective study of 700 SARS-CoV-2 vaccinated individuals and 303 unvaccinated individuals who underwent FDG PET at our hospital over a one-year and four-month period starting in fiscal year 2020. Compared to the unvaccinated group, the vaccinated group showed significantly higher myocardial FDG uptake, regardless of sex, age, or type of mRNA vaccine. When stratified by the number of days since vaccination, increased axillary uptake was significant for up to 120 days, and myocardial FDG uptake remained significantly high for up to 180 days post-vaccination. Although it is uncertain whether the myocardial FDG uptake reflects inflammation or metabolic enhancement, we have shown that SARS-CoV-2 vaccination increases myocardial FDG uptake. The journal in which it was published is a top journal in diagnostic imaging. Just two months after publication, it became the most viewed paper to date, and the journal's editorial board recognized it as having a view count that was "by far the top," which is displayed on their website.

(Masahiro Jinzaki, Professor, Department of Diagnostic Radiology, 66th class; Takehiro Nakahara, Project Senior Assistant Professor／Project Assistant Professor／Project Lecturer, equivalent to the 82nd class; Yu Iwabuchi, Senior Assistant Professor, 86th class)

Adv Sci (Weinh).

2023 Oct 17:e2301831. doi: 10.1002/advs.202301831

Yuta Kurashina, Keisuke Fukada, Shun Itai, Shuichi Akizuki, Ryo Sato, Akari Masuda, Hidenori Tani, Jun Fujita, Keiichi Fukuda, Shugo Tohyama, Hiroaki Onoe