Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis-Reference-Cited by-同舟云学术

Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis

Published:2023-09-29 Issue:6665 Volume:381 Page:1480-1487
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Wang Yijie¹²³⁴⁵^ORCID,Li Qihao⁶,Tao Bo¹²³⁴⁵,Angelini Marina⁷,Ramadoss Sivakumar¹²³⁴⁵,Sun Baiming¹²³⁴⁵,Wang Ping¹²³⁴⁵^ORCID,Krokhaleva Yuliya⁸^ORCID,Ma Feiyang⁹^ORCID,Gu Yiqian³¹⁰^ORCID,Espinoza Alejandro³¹⁰^ORCID,Yamauchi Ken⁴¹¹,Pellegrini Matteo³¹⁰^ORCID,Novitch Bennett⁴¹¹^ORCID,Olcese Riccardo⁷¹²,Qu Zhilin¹^ORCID,Song Zhen⁶^ORCID,Deb Arjun¹²³⁴⁵^ORCID

Affiliation:

1. Division of Cardiology, Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

2. Cardiovascular Theme, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

3. Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.

4. Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA.

5. Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.

6. Peng Cheng Laboratory, Shenzhen, Guangdong 518000, China.

7. Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

8. UCLA Cardiac Arrhythmia Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

9. Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

10. Institute for Quantitative and Computational Biosciences–The Collaboratory, University of California Los Angeles, Los Angeles, CA 90095, USA.

11. Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

12. Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

Abstract

After heart injury, dead heart muscle is replaced by scar tissue. Fibroblasts can electrically couple with myocytes, and changes in fibroblast membrane potential can lead to myocyte excitability, which suggests that fibroblast-myocyte coupling in scar tissue may be responsible for arrhythmogenesis. However, the physiologic relevance of electrical coupling of myocytes and fibroblasts and its impact on cardiac excitability in vivo have never been demonstrated. We genetically engineered a mouse that expresses the optogenetic cationic channel ChR2 (H134R) exclusively in cardiac fibroblasts. After myocardial infarction, optical stimulation of scar tissue elicited organ-wide cardiac excitation and induced arrhythmias in these animals. Complementing computational modeling with experimental approaches, we showed that gap junctional and ephaptic coupling, in a synergistic yet functionally redundant manner, excited myocytes coupled to fibroblasts.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.adh9925

Reference55 articles.

1. Systematic Characterization of Myocardial Inflammation, Repair, and Remodeling in a Mouse Model of Reperfused Myocardial Infarction

2. The extracellular matrix in myocardial injury, repair, and remodeling

3. A review of the literature on cardiac electrical activity between fibroblasts and myocytes

4. Cardiac fibrosis and arrhythmogenesis: The road to repair is paved with perils

5. Arrhythmogenic consequences of myofibroblast–myocyte coupling

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