JACC: Basic to Translational Science (Oct 2019)
Cardioprotective Effects of VCP Modulator KUS121 in Murine and Porcine Models of Myocardial Infarction
- Yuya Ide, MD,
- Takahiro Horie, MD, PhD,
- Naritatsu Saito, MD, PhD,
- Shin Watanabe, MD, PhD,
- Chiharu Otani, MD,
- Yui Miyasaka, BSc,
- Yasuhide Kuwabara, MD, PhD,
- Tomohiro Nishino, MD, PhD,
- Tetsushi Nakao, MD, PhD,
- Masataka Nishiga, MD, PhD,
- Hitoo Nishi, MD, PhD,
- Yasuhiro Nakashima, MD, PhD,
- Fumiko Nakazeki, MD, PhD,
- Satoshi Koyama, MD, PhD,
- Masahiro Kimura, MD,
- Shuhei Tsuji, MD,
- Randolph Ruiz Rodriguez, MD,
- Sijia Xu, MD,
- Tomohiro Yamasaki, MD,
- Toshimitsu Watanabe, MD,
- Masamichi Yamamoto, PhD,
- Motoko Yanagita, MD, PhD,
- Takeshi Kimura, MD, PhD,
- Akira Kakizuka, MD, PhD,
- Koh Ono, MD, PhD
Affiliations
- Yuya Ide, MD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Takahiro Horie, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Naritatsu Saito, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Shin Watanabe, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Chiharu Otani, MD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Yui Miyasaka, BSc
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Yasuhide Kuwabara, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Tomohiro Nishino, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Tetsushi Nakao, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Masataka Nishiga, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Hitoo Nishi, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Yasuhiro Nakashima, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Fumiko Nakazeki, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Satoshi Koyama, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Masahiro Kimura, MD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Shuhei Tsuji, MD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Randolph Ruiz Rodriguez, MD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Sijia Xu, MD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Tomohiro Yamasaki, MD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Toshimitsu Watanabe, MD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Masamichi Yamamoto, PhD
- Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Motoko Yanagita, MD, PhD
- Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Institute for the Advanced Study of Human Biology, Kyoto University, Kyoto, Japan
- Takeshi Kimura, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Akira Kakizuka, MD, PhD
- Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies and Solution Oriented Research for Science and Technology, Kyoto, Japan; Dr. Akira Kakizuka, Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies and Solution Oriented Research for Science and Technology, Kyoto 606-8501, Japan.
- Koh Ono, MD, PhD
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan; Address for correspondence: Dr. Koh Ono, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
- Journal volume & issue
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Vol. 4,
no. 6
pp. 701 – 714
Abstract
Summary: No effective treatment is yet available to reduce infarct size and improve clinical outcomes after acute myocardial infarction by enhancing early reperfusion therapy using primary percutaneous coronary intervention. The study showed that Kyoto University Substance 121 (KUS121) reduced endoplasmic reticulum stress, maintained adenosine triphosphate levels, and ameliorated the infarct size in a murine cardiac ischemia and reperfusion injury model. The study confirmed the cardioprotective effect of KUS121 in a porcine ischemia and reperfusion injury model. These findings confirmed that KUS121 is a promising novel therapeutic agent for myocardial infarction in conjunction with primary percutaneous coronary intervention. Key Words: ATP, ER stress, KUS121, myocardial infarction
