Takashi Matsui, MD, PhD
Chair, Department of Anatomy, Biochemistry and Physiology
Deputy Director, Center for Cardiovascular Research (CCR)
The Matsui Lab is focused on the insulin signaling pathway in cardiomyocytes, especially cardioprotective effects against pathological settings such as ischemia. Our interests center around the role of the mechanistic target of rapamycin (mTOR), which is intimately related to the insulin/phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathway. In order to investigate the role of mTOR in the heart, we utilize a variety of in vitro, in vivo, and ex vivo models of heart failure with genetically manipulated models of mTOR such as transgenic and knockout mice. We have reported that the role of cardiac mTOR in prevention of cardiomyocyte cell death that arises from myocardial infarction and cardiac hypertrophy, apparent risk factors for heart failure.
Diabetes is an independent risk factor for both heart failure and ischemic heart disease. Because of the important role of mTOR in insulin signaling, we have been working to determine the role of mTOR in diabetic hearts, and exploring the mTOR signaling pathway as a novel therapeutic target for treatment of heart failure in diabetes.
Recently Dr. Matsui’s laboratory demonstrated that mTOR is necessary and sufficient for cardiomyocyte protection against iron-mediated cell death that includes excessive iron-induced cell death and ferroptosis that is an iron-dependent form of regulated cell death. This is the first report that ferroptosis is a significant type of cell death in cardiomyocytes. We are currently defining the pathophysiological role of ferroptosis in cardiac diseases such as acute myocardial infarction and heart failure.
- Mishra PK, Adameova A, Hill AJ, Baines CP, Kang P, Dawney JM, Narula J, Takahashi M, Abbate A, Piristine H, Su S, Higa JK, Kawasaki NK, Matsui T. Guidelines for evaluating myocardial cell death. Am J Physiol Heart Circ Physiol 317: H891-H922, 2019. doi: 10.1152/ajpheart.00259.2019. PMID: 3141859
- Yorichika N, Baba Y, Shimada BK, Thakore M, Wong SM, Kobayashi M, Higa JK, Matsui T*. The effects of Tel2 on cardiomyocyte survival. Life Sci. 2019 Sep 1;232:116665. doi: 10.1016/j.lfs.2019.116665. Epub 2019 Jul 16. PMID: 31323273
- Kobayashi M, Suhara T, Baba Y, Kawasaki KK, Higa JK, Matsui T*. Pathological roles of iron in cardiovascular disease. Curr Drug Targets. 2018;19(9):1068-1076. doi: 10.2174/1389450119666180605112235.
- Baba Y, Higa JK, Shimada BK, Horiuchi KM, Suhara T, Kobayashi M, Woo JD, Aoyagi H, Marh KS, Kitaoka H, Matsui T*. Protective effects of the mechanistic target of rapamycin against excess iron and ferroptosis in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2018;314:H659-H668 [selected in Editor Picked Articles and posted on Podcast]
- Suhara T, Baba Y, Shimada BK, Higa JK, Matsui T*. The mTOR signaling pathway in myocardial dysfunction in type 2 diabetes mellitus. Curr Diab Rep. 2017;17(6):38.
- Aoyagi T, Higa JK, Aoyagi H, Yorichika N, Shimada BK, Matsui T*. Cardiac mTOR rescues the detrimental effects of diet-induced obesity in the heart after ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2015;308(12):H1530-1539.
- Katz MY, Kusakari Y, Aoyagi H, Higa JK, Xiao C-Y, Abdelkarim AZ, Marh K, Aoyagi A, Rosenzweig A, Lozanoff S, Matsui T*. Three dimensional myocardial scarring along myofibers after coronary ischemia-reperfusion revealed by computerized images of histological assays. Physiol Rep. 2014;2 (7): e12072 (open-access article), doi: 10.14814/phy2.12072.
- Aoyagi T, Kusakari Y, Xiao C-Y, Inouye BT, Takahashi M, Scherrer-Crosbie M, Rosenzweig A, Hara K, Matsui T*. Cardiac mTOR protects the heart against ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2012;303(1):H75-85.
- Song X, Kusakari Y, Xiao C-Y, Kinsella SD, Rosenberg MA, Scherrer-Crosbie M, Hara K, Rosenzweig A, Matsui T*. mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy. Am J Physiol Cell Physiol. 2010;299(6):C1256-66.
- Matsui T*, Nagoshi T, Hong EG, Luptak I, Hartil K, Li L, Gorovits N, Charron MJ, Kim JK, Tian R, Rosenzweig A. The effects of chronic Akt activation on glucose uptake in the heart. Am J Physiol Endocrinol Metab. 2006;290:E789-97.
- Higa JK, Kawasaki NK, Matsui T*. Ferroptosis in Cardiovascular Disease. In: Daolin Tang, editor. Ferroptosis in Health and Disease. Springer Nature; 2019.
- Matsui T*. Role of Caspases in Apoptotic-Driven Indications. In: Tom O’Brien and Steven D. Linton, editors. Design of Caspase Inhibitors as Potential Clinical Agents. Boca Raton, FL: Taylor & Francis Group; 2008, p59-73