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

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

JACC: Basic to Translational Science (Sep 2019)

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

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

Affiliations

Shohei Ikeda, MD, PhD: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey; Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
Risa Mukai, MD, PhD: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey
Wataru Mizushima, MD, PhD: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey
Peiyong Zhai, MD, PhD: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey
Shin-ichi Oka, PhD: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey
Michinari Nakamura, MD, PhD: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey
Dominic P. Del Re, PhD: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey
Sebastiano Sciarretta, MD, PhD: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; Istituto Di Ricovero e Cura a Carattere Scientifico Neuromed, Pozzilli, Italy
Chiao-Po Hsu, MD, PhD: Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, Taiwan
Hiroaki Shimokawa, MD, PhD: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
Junichi Sadoshima, MD, PhD: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey; Address for correspondence: Dr. Junichi Sadoshima, Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, 185 South Orange Avenue, MSB G609, Newark, New Jersey 07103.

Journal volume & issue: Vol. 4, no. 5
pp. 611 – 622

Abstract

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Summary: 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. Key Words: diabetes, diabetic cardiomyopathy, Hippo pathway, pressure overload

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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