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The role of Epac in the heart

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Abstract

As one of the most important second messengers, 3′,5′-cyclic adenosine monophosphate (cAMP) mediates various extracellular signals including hormones and neurotransmitters, and induces appropriate responses in diverse types of cells. Since cAMP was formerly believed to transmit signals through only two direct target molecules, protein kinase A and the cyclic nucleotide-gated channel, the sensational discovery in 1998 of another novel direct effecter of cAMP [exchange proteins directly activated by cAMP (Epac)] attracted a great deal of scientific interest in cAMP signaling. Numerous studies on Epac have since disclosed its important functions in various tissues in the body. Recently, observations of genetically manipulated mice in various pathogenic models have begun to reveal the in vivo significance of previous in vitro or cellular-level findings. Here, we focused on the function of Epac in the heart. Accumulating evidence has revealed that both Epac1 and Epac2 play important roles in the structure and function of the heart under physiological and pathological conditions. Accordingly, developing the ability to regulate cAMP-mediated signaling through Epac may lead to remarkable new therapies for the treatment of cardiac diseases.

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Acknowledgments

This study has been supported in part by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grants (25460296, 24390200, 25670131), The Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI Grant (22136009), the New Energy and Industrial Technology Development Organization (NEDO) (60890021), the National Cerebral and Cardiovascular Center (NCVC) (22-2-3), the Japan Agency for Medical Research and Development (AMED) (66890005, 66890011, 66890001, 66890023), and a Grant for Strategic Research Promotion of Yokohama City University. The authors are grateful to Ms. Nana Fujita for improving the figures.

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  1. Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Takayuki Fujita, Masanari Umemura, Utako Yokoyama, Satoshi Okumura & Yoshihiro Ishikawa

  2. Tsurumi University School of Dental Medicine, Yokohama, Japan

    Satoshi Okumura

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  1. Takayuki Fujita
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  2. Masanari Umemura
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Correspondence to Takayuki Fujita or Yoshihiro Ishikawa.

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Fujita, T., Umemura, M., Yokoyama, U. et al. The role of Epac in the heart. Cell. Mol. Life Sci. 74, 591–606 (2017). https://doi.org/10.1007/s00018-016-2336-5

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