The Degradation systems in the genesis of heart failure
By Professor Kinya Otsu, President, National Cerebral and Cardiovascular Center, Emeritus British Heart Foundation Chair of Cardiology and Adjunct Honorary Professor of Cardiology, King’s College London.
Heart failure is a major cause of morbidity and mortality despite advances in its management. The mechanisms underlying the development of heart failure are multiple, complex, and not well understood. Cardiomyocyte death, including apoptosis, necrosis, and autophagic cell death, as well as inflammation and their vicious cycle, plays a crucial role in the genesis of heart failure. Cellular homeostasis is maintained by the balance between molecular synthesis and degradation, and an imbalance is likely to result in cellular dysfunction, cardiomyocyte death, and inflammation. We have been investigating the role of all types of cardiomyocyte death and inflammation in the genesis of heart failure. Pressure overload results in the accumulation of damaged mitochondria, which are degraded by the autophagic system (mitophagy). DNase I in lysosomes and cytosolic RNase regulate the development and maintenance of cardiac inflammation. In my talk, I will discuss the importance of degradation systems, including lipid degradation and selective autophagy, such as ferritinophagy and mitophagy, in cardiac pathology.
References
1: Ito J, et al. Iron derived from autophagy-mediated ferritin degradation induces cardiomyocyte death and heart failure in mice. Elife. 2021;10:e62174.
2: Sugihara R, et al. Lysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein-coupled receptor 34. Nat Commun. 2023;14(1):4494.
3: Murakawa T, et al. AMPK regulates Bcl2-L-13-mediated mitophagy induction for cardioprotection. Cell Rep. 2024;43(12):115001.
A short bio
Professor Kinya Otsu graduated from Osaka University Medical School, Japan and received his MD in 1983. Following two years training in residency in Internal Medicine, he began his career in cardiovascular research at the National Institute of Health, USA (1984-1988) followed by the University of Toronto, Canada (1988-1991) and University of Nice, France (1991). He moved back to Japan as a Senior Resident in Cardiology at the Osaka University Hospital. He was appointed as Assistant Professor in 1997 and subsequently as Associate Professor of Cardiology in 2005 at the Osaka University Graduate School of Medicine. In 2012, he was recruited from Osaka to London as Professor of Cardiology at King’s College London and became a BHF Chair of Cardiology. In 2021, he was appointed as President of National Cerebral and Cardiovascular Center, Japan.
A brief overview of the National Cerebral and Cardiovascular Center (NCVC).
The National Cerebral and Cardiovascular Center (NCVC) is Japan’s most advanced medical institution specializing in cardiovascular and cerebral diseases, with approximately 2,000 staff members working there. The Center has three divisions: the Hospital, the Research Institute, and the Open Innovation Center, which facilitates collaborative research with companies and universities. These divisions operate as one cohesive organization. The Center promotes prevention, diagnosis, treatment, and elucidation of the pathophysiology of the diseases. It also plays a significant role in educating young medical professionals from across Japan and the world. As to the research institute, it comprises 18 Departments and various laboratories, ranging from basic to translational research (https://www.ncvc.go.jp/english/res/department/).