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Loss of Caveolin-1 and caveolae leads to increased cardiac cell stiffness and functional decline of the adult zebrafish heart

Dimitrios Grivas, Álvaro González-Rajal, Carlos Guerrero Rodríguez, Ricardo Garcia, View ORCID ProfileJosé Luis de la Pompa
doi: https://doi.org/10.1101/2020.01.16.909267
Dimitrios Grivas
1Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid 28029, Spain
2Ciber de Enfermedades Cardiovasculares, 28029 Madrid, Spain
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Álvaro González-Rajal
1Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid 28029, Spain
3Cell Division Lab, ANZAC Research Institute, Gate 3, Hospital Road, Concord 2139, NSW, Australia
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Carlos Guerrero Rodríguez
4Materials Science Factory, Instituto de Ciencia de Materiales de Madrid (ICMM), CSIC, 28049 Madrid, Spain
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Ricardo Garcia
4Materials Science Factory, Instituto de Ciencia de Materiales de Madrid (ICMM), CSIC, 28049 Madrid, Spain
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José Luis de la Pompa
1Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid 28029, Spain
2Ciber de Enfermedades Cardiovasculares, 28029 Madrid, Spain
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  • ORCID record for José Luis de la Pompa
  • For correspondence: jlpompa@cnic.es
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ABSTRACT

Caveolin-1 is the main structural protein of caveolae, small membrane invaginations involved in signal transduction and mechanoprotection. Here, we generated cav1-KO zebrafish lacking Cav1 and caveolae, and investigated the impact of this loss on adult heart function and response to cryoinjury. We found that cardiac function was impaired in adult cav1-KO fish, which showed a significantly decreased ejection fraction and heart rate. Using atomic force microscopy, we detected an increase in the stiffness of epicardial cells and cortical myocardium lacking Cav1/caveolae. This loss of cardiac elasticity might explain the decreased cardiac contraction and function. Surprisingly, cav1-KO mutants were able to regenerate their heart after a cryoinjury but showed a transient decrease in cardiomyocyte proliferation.

Footnotes

  • Summary statement We have generated cav1-KO zebrafish strains that lack caveolae. We found that cardiac function is impaired and that the stiffness of epicardial cells and cortical myocardium is increased.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 16, 2020.
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Loss of Caveolin-1 and caveolae leads to increased cardiac cell stiffness and functional decline of the adult zebrafish heart
Dimitrios Grivas, Álvaro González-Rajal, Carlos Guerrero Rodríguez, Ricardo Garcia, José Luis de la Pompa
bioRxiv 2020.01.16.909267; doi: https://doi.org/10.1101/2020.01.16.909267
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Loss of Caveolin-1 and caveolae leads to increased cardiac cell stiffness and functional decline of the adult zebrafish heart
Dimitrios Grivas, Álvaro González-Rajal, Carlos Guerrero Rodríguez, Ricardo Garcia, José Luis de la Pompa
bioRxiv 2020.01.16.909267; doi: https://doi.org/10.1101/2020.01.16.909267

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