TRPC3 Channels in Cardiac Fibrosis
Autor: | Takuro Numaga-Tomita, Sayaka Oda, Tsukasa Shimauchi, Akiyuki Nishimura, Supachoke Mangmool, Motohiro Nishida |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
medicine.medical_specialty lcsh:Diseases of the circulatory (Cardiovascular) system Cardiac fibrosis cardiac fibrosis Regulator Review Cardiovascular Medicine 03 medical and health sciences Transient receptor potential channel TRPC3 Mediator Internal medicine medicine TRPC reactive oxygen species NADPH oxidase biology medicine.disease Cell biology Ca2+ 030104 developmental biology Endocrinology lcsh:RC666-701 biology.protein cardiac remodeling Cardiology and Cardiovascular Medicine Heart failure with preserved ejection fraction canonical transient receptor potential |
Zdroj: | Frontiers in Cardiovascular Medicine, Vol 4 (2017) Frontiers in Cardiovascular Medicine |
Popis: | Cardiac stiffness, caused by interstitial fibrosis due to deposition of extracellular matrix proteins, is thought as a major clinical outcome of heart failure with preserved ejection fraction (HFpEF). Canonical transient receptor potential (TRPC) subfamily proteins are components of Ca2+-permeable non-selective cation channels activated by receptor stimulation and mechanical stress, and have been attracted attention as a key mediator of maladaptive cardiac remodeling. How TRPC-mediated local Ca2+ influx encodes a specific signal to induce maladaptive cardiac remodeling has been long obscure, but our recent studies suggest a pathophysiological significance of channel activity-independent function of TRPC proteins for amplifying redox signaling in heart. This review introduces the current understanding of the physiological and pathophysiological roles of TRPCs, especially focuses on the role of TRPC3 as a positive regulator of reactive oxygen species (PRROS) in heart. We have revealed that TRPC3 stabilizes NADPH oxidase 2 (Nox2), a membrane-bound reactive oxygen species (ROS)-generating enzyme, by forming stable protein complex with Nox2, which leads to amplification of mechanical stress-induced ROS signaling in cardiomyocytes, resulting in induction of fibrotic responses in cardiomyocytes and cardiac fibroblasts. Thus, the TRPC3 function as PRROS will offer a new therapeutic strategy for the prevention or treatment of HFpEF. |
Databáze: | OpenAIRE |
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