Increased length-dependent activation of human engineered heart tissue after chronic α<sub>1A</sub>-adrenergic agonist treatment: testing a novel heart failure therapy-Reference-Cited by-同舟云学术

Increased length-dependent activation of human engineered heart tissue after chronic α_1A-adrenergic agonist treatment: testing a novel heart failure therapy

Published:2023-03-01 Issue:3 Volume:324 Page:H293-H304
ISSN:0363-6135
Container-title:American Journal of Physiology-Heart and Circulatory Physiology
language:en
Short-container-title:American Journal of Physiology-Heart and Circulatory Physiology

Author:

Rupert C.¹^ORCID,López J. E.²,Cortez-Toledo E.²,De la Cruz Cabrera O.³^ORCID,Chesler N. C.⁴⁵^ORCID,Simpson P. C.⁶⁷,Campbell S. G.⁸^ORCID,Baker A. J.⁶⁷^ORCID

Affiliation:

1. Propria LLC, Branford, Connecticut, United States

2. Division of Cardiovascular Medicine, Department of Internal Medicine, University of California Davis, Davis, California, United States

3. Kent State University, Kent, Ohio, United States

4. Edwards Lifesciences Foundation Cardiovascular Innovation Research Center, Irvine, California, United States

5. Department of Biomedical Engineering, University of California, Irvine, California, United States

6. Cardiology Division, Veterans Affairs Medical Center, San Francisco, California, United States

7. Department of Medicine, University of California, San Francisco, California, United States

8. Departments of Biomedical Engineering and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, United States

Abstract

Chronic stimulation of α1A-adrenergic receptors (α1A-ARs) is known to mediate therapeutic effects in animal heart failure models. To investigate the effects of chronic α1A-AR stimulation in human cardiomyocytes, we tested engineered heart tissue (EHT) created with iPSC-derived cardiomyocytes. RNA-seq analysis confirmed human EHT expressed α1A-ARs. Chronic (2 wk) α1A-AR stimulation with A61603 (10 nM) increased length-dependent activation (LDA) of contraction. Chronic α1A-AR stimulation might be beneficial for treating human heart failure by restoring LDA.

Funder

Harold S. Geneen Charitable Trust

HHS | NIH | National Heart, Lung, and Blood Institute

HHS | NIH | NIH Office of the Director

U.S. Department of Veterans Affairs

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

Link

https://journals.physiology.org/doi/pdf/10.1152/ajpheart.00279.2022

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