Yes-Associated Protein (YAP) Facilitates Pressure Overload–Induced Dysfunction in the Diabetic Heart

Shohei Ikeda; Risa Mukai; Wataru Mizushima; Peiyong Zhai; Shin ichi Oka; Michinari Nakamura; Dominic P. Del Re; Sebastiano Sciarretta; Chiao Po Hsu; Hiroaki Shimokawa; Junichi Sadoshima

doi:10.1016/j.jacbts.2019.05.006

Yes-Associated Protein (YAP) Facilitates Pressure Overload–Induced Dysfunction in the Diabetic Heart

Shohei Ikeda, Risa Mukai, Wataru Mizushima, Peiyong Zhai, Shin ichi Oka, Michinari Nakamura, Dominic P. Del Re, Sebastiano Sciarretta, Chiao Po Hsu, Hiroaki Shimokawa, Junichi Sadoshima

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Patients with diabetes are more prone to developing heart failure in the presence of high blood pressure than those without diabetes. Yes-associated protein (YAP), a key effector of the Hippo signaling pathway, is persistently activated in diabetic hearts, and YAP plays an essential role in mediating the exacerbation of heart failure in response to pressure overload in the hearts of mice fed a high-fat diet. YAP induced dedifferentiation of cardiomyocytes through activation of transcriptional enhancer factor 1 (TEAD1), a transcription factor. Thus, YAP and TEAD1 are promising therapeutic targets for diabetic patients with high blood pressure to prevent the development of heart failure.

Original language	English (US)
Pages (from-to)	611-622
Number of pages	12
Journal	JACC: Basic to Translational Science
Volume	4
Issue number	5
DOIs	https://doi.org/10.1016/j.jacbts.2019.05.006
State	Published - Sep 2019

All Science Journal Classification (ASJC) codes

Cardiology and Cardiovascular Medicine

Keywords

Hippo pathway
diabetes
diabetic cardiomyopathy
pressure overload

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10.1016/j.jacbts.2019.05.006

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title = "Yes-Associated Protein (YAP) Facilitates Pressure Overload–Induced Dysfunction in the Diabetic Heart",

abstract = "Patients with diabetes are more prone to developing heart failure in the presence of high blood pressure than those without diabetes. Yes-associated protein (YAP), a key effector of the Hippo signaling pathway, is persistently activated in diabetic hearts, and YAP plays an essential role in mediating the exacerbation of heart failure in response to pressure overload in the hearts of mice fed a high-fat diet. YAP induced dedifferentiation of cardiomyocytes through activation of transcriptional enhancer factor 1 (TEAD1), a transcription factor. Thus, YAP and TEAD1 are promising therapeutic targets for diabetic patients with high blood pressure to prevent the development of heart failure.",

keywords = "Hippo pathway, diabetes, diabetic cardiomyopathy, pressure overload",

author = "Shohei Ikeda and Risa Mukai and Wataru Mizushima and Peiyong Zhai and Oka, {Shin ichi} and Michinari Nakamura and {Del Re}, {Dominic P.} and Sebastiano Sciarretta and Hsu, {Chiao Po} and Hiroaki Shimokawa and Junichi Sadoshima",

note = "Funding Information: Dr. Sadoshima was supported in part by U.S. Public Health Service grants HL67724, HL91469, HL11233, HL132824, and AG23039, and by the Leducq Foundation Transatlantic Network of Excellence (15CBD04). Dr. Ikeda has been supported by a postdoctoral fellowship from the Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad and grants-in-aid for scientific research (18K15876). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = sep,

doi = "10.1016/j.jacbts.2019.05.006",

language = "English (US)",

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T1 - Yes-Associated Protein (YAP) Facilitates Pressure Overload–Induced Dysfunction in the Diabetic Heart

AU - Ikeda, Shohei

AU - Mukai, Risa

AU - Mizushima, Wataru

AU - Zhai, Peiyong

AU - Oka, Shin ichi

AU - Nakamura, Michinari

AU - Del Re, Dominic P.

AU - Sciarretta, Sebastiano

AU - Hsu, Chiao Po

AU - Shimokawa, Hiroaki

AU - Sadoshima, Junichi

N1 - Funding Information: Dr. Sadoshima was supported in part by U.S. Public Health Service grants HL67724, HL91469, HL11233, HL132824, and AG23039, and by the Leducq Foundation Transatlantic Network of Excellence (15CBD04). Dr. Ikeda has been supported by a postdoctoral fellowship from the Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad and grants-in-aid for scientific research (18K15876). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2019

PY - 2019/9

Y1 - 2019/9

N2 - Patients with diabetes are more prone to developing heart failure in the presence of high blood pressure than those without diabetes. Yes-associated protein (YAP), a key effector of the Hippo signaling pathway, is persistently activated in diabetic hearts, and YAP plays an essential role in mediating the exacerbation of heart failure in response to pressure overload in the hearts of mice fed a high-fat diet. YAP induced dedifferentiation of cardiomyocytes through activation of transcriptional enhancer factor 1 (TEAD1), a transcription factor. Thus, YAP and TEAD1 are promising therapeutic targets for diabetic patients with high blood pressure to prevent the development of heart failure.

AB - Patients with diabetes are more prone to developing heart failure in the presence of high blood pressure than those without diabetes. Yes-associated protein (YAP), a key effector of the Hippo signaling pathway, is persistently activated in diabetic hearts, and YAP plays an essential role in mediating the exacerbation of heart failure in response to pressure overload in the hearts of mice fed a high-fat diet. YAP induced dedifferentiation of cardiomyocytes through activation of transcriptional enhancer factor 1 (TEAD1), a transcription factor. Thus, YAP and TEAD1 are promising therapeutic targets for diabetic patients with high blood pressure to prevent the development of heart failure.

KW - Hippo pathway

KW - diabetes

KW - diabetic cardiomyopathy

KW - pressure overload

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Yes-Associated Protein (YAP) Facilitates Pressure Overload–Induced Dysfunction in the Diabetic Heart

Abstract

All Science Journal Classification (ASJC) codes

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