1: RIP140 deficiency enhances cardiac fuel metabolism and protects mice from heart failure
Science of the Month - April 2023
J Clin Invest.
2023 Mar 16;e162309. doi: 10.1172/JCI162309.
Tsunehisa Yamamoto, Santosh K Maurya, Elizabeth Pruzinsky, Kirill Batmanov, Yang Xiao, Sarah M Sulon, Tomoya Sakamoto, Yang Wang, Ling Lai, Kendra S McDaid, Swapnil V Shewale, Teresa C Leone, Timothy R Koves, Deborah M Muoio, Pieterjan Dierickx, Mitchell A Lazar, E Douglas Lewandowski, Daniel P Kelly
Heart failure is a condition in which the heart's pumping function is reduced, making it unable to deliver enough blood to meet the needs of the body's organs. It is the most common form of heart disease, which is the second leading cause of death in Japan. It is known that in heart failure, the function of factors crucial for fatty acid metabolism and mitochondrial function regulation, such as the nuclear receptors PPAR and ERR, as well as the co-activator PGC-1α, is impaired, contributing to the decline in the heart's pumping function. In this study, the authors focused on the co-repressor Receptor Interacting Protein 140 (RIP140) as an endogenous regulator of PPAR/ERR in the heart. They found that in RIP140-deficient hearts, PPAR/ERR-mediated fatty acid metabolism and mitochondrial function were enhanced. Furthermore, by restoring the function of physiological myocardial contractile proteins through mTORC, these hearts showed resistance to pressure overload-induced pathological left ventricular remodeling and heart failure. The findings of this study are expected to lead to the creation of new therapeutic strategies for heart failure, such as screening for small molecule compounds that modify the function of RIP140.
(Tsunehisa Yamamoto, Department of Cardiology, 88th)
2: Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers.
Cancer Research.
Namba S, Saito Y, Kogure Y, Masuda T, Bondy ML, Gharahkhani P, Gockel I, Heider D, Hillmer A, Jankowski J, MacGregor S, Maj C, Melin B, Ostrom QT, Palles C, Schumacher J, Tomlinson I, Whiteman DC, Okada Y, Kataoka K.
In addition to various environmental factors, genetic factors are important in the development of cancer. In recent years, genome-wide association studies have revealed that hundreds to thousands of SNPs common in the population influence cancer development. Although each of these SNPs confers a low individual risk of cancer, their cumulative effect across the genome is known to be significant due to their large number (hundreds to thousands). Therefore, it is thought that by evaluating these SNPs collectively, it is possible to assess an individual's "genetic predisposition to cancer risk" (a genetic constitution that makes one more susceptible to cancer). We comprehensively evaluated the impact of genetic cancer risk on cancer characteristics by calculating polygenic risk scores, an indicator reflecting genetic predisposition to cancer risk, for approximately 3,000 cancer patients. The results revealed that across various cancer types, individuals with a high genetic predisposition to cancer risk tend to develop cancer at a younger age and before a large number of somatic mutations or copy number abnormalities have accumulated.
(Yuki Saito, Department of Internal Medicine (Gastroenterology), 94th)
Other Published Papers
1: An epithelial-immune circuit amplifies inflammasome and IL-6 responses to SARS-CoV-2 Cell Host and Microbe, 31(2), 243-259.e6.
Cell Host and Microbe,
Barnett, K. C., Xie, Y., Asakura, T., Song, D., Liang, K., Taft-Benz, S. A., Guo, H., Yang, S., Okuda, K., Gilmore, R. C., Loome, J. F., Oguin Iii, T. H., Sempowski, G. D., Randell, S. H., Heise, M. T., Lei, Y. L., Boucher, R. C., & Ting, J. P-Y.
2: Language patterns in Japanese patients with Alzheimer disease: A machine learning approach.
Psychiatry Clin Neurosci.
Momota, Y., Liang, K., Horigome, T., Kitazawa, M., Eguchi, Y., Takamiya, A., Goto, A., Mimura, M., Kishimoto, T.
Psychiatry Clin. Neurosci. 2023.
3: Balloon pulmonary angioplasty versus riociguat in inoperable chronic thromboembolic pulmonary hypertension (MR BPA) an open-label, randomised controlled trial.
Lancet Respiratory Medicine.
Kawakami T, Matsubara H, Shinke T, Abe K, Kohsaka S, Hosokawa K, Taniguchi Y, Shimokawahara H, Yamada Y, Kataoka M, Ogawa A, Murata M, Jinzaki M, Hirata K, Tsutsui H, Sato Y, Fukuda K.