Endocardial TRPC-6 Act as Atrial Mechanosensors and Load-Dependent Modulators of Endocardial/Myocardial Cross-Talk

Vesna Nikolova-Krstevski, PhD; Soeren Wagner, MD; Ze Yan Yu, MD; Charles D. Cox, PhD; Jasmina Cvetkovska, BSc; Adam P. Hill, PhD; Inken G. Huttner, MD; Victoria Benson, PhD; Andreas A. Werdich, PhD; Calum MacRae, MD, PhD; Michael P. Feneley, MD, PhD; Oliver Friedrich, PhD; Boris Martinac, PhD; Diane Fatkin, MD

doi:10.1016/j.jacbts.2017.05.006

JACC: Basic to Translational Science (Oct 2017)

Endocardial TRPC-6 Act as Atrial Mechanosensors and Load-Dependent Modulators of Endocardial/Myocardial Cross-Talk

Vesna Nikolova-Krstevski, PhD,
Soeren Wagner, MD,
Ze Yan Yu, MD,
Charles D. Cox, PhD,
Jasmina Cvetkovska, BSc,
Adam P. Hill, PhD,
Inken G. Huttner, MD,
Victoria Benson, PhD,
Andreas A. Werdich, PhD,
Calum MacRae, MD, PhD,
Michael P. Feneley, MD, PhD,
Oliver Friedrich, PhD,
Boris Martinac, PhD,
Diane Fatkin, MD

Affiliations

Vesna Nikolova-Krstevski, PhD: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
Soeren Wagner, MD: Department of Anesthesiology, University Clinic Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
Ze Yan Yu, MD: St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Kensington, New South Wales, Australia
Charles D. Cox, PhD: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
Jasmina Cvetkovska, BSc: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
Adam P. Hill, PhD: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
Inken G. Huttner, MD: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
Victoria Benson, PhD: Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
Andreas A. Werdich, PhD: Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
Calum MacRae, MD, PhD: Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
Michael P. Feneley, MD, PhD: St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Kensington, New South Wales, Australia
Oliver Friedrich, PhD: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
Boris Martinac, PhD: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
Diane Fatkin, MD: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia

DOI: https://doi.org/10.1016/j.jacbts.2017.05.006
Journal volume & issue: Vol. 2, no. 5
pp. 575 – 590

Abstract

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Mechanoelectrical feedback may increase arrhythmia susceptibility, but the molecular mechanisms are incompletely understood. This study showed that mechanical stretch altered the localization, protein levels, and function of the cation-selective transient receptor potential channel (TRPC)-6 in atrial endocardial cells in humans, pigs, and mice. In endocardial/myocardial cross-talk studies, addition of media from porcine atrial endocardium (AE) cells altered the calcium (Ca2+) transient characteristics of human-induced pluripotent stem cell-derived cardiomyocytes. These changes did not occur with media from stretched AE cells. Our data suggested that endocardial TRPC-6-dependent paracrine signaling may modulate myocardial Ca2+ homeostasis under basal conditions and protect against stretch-induced atrial arrhythmias.

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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