PUBLICATION
Mechanical forces remodel the cardiac extracellular matrix during zebrafish development
- Authors
- Gentile, A., Albu, M., Xu, Y., Mortazavi, N., Ribeiro da Silva, A., Stainier, D.Y.R., Gunawan, F.
- ID
- ZDB-PUB-240711-1
- Date
- 2024
- Source
- Development (Cambridge, England) 151(13): (Journal)
- Registered Authors
- Albu, Marga, Stainier, Didier
- Keywords
- Biomechanical forces, Cardiac ECM remodeling, Cardiac development, Zebrafish cardiogenesis
- MeSH Terms
-
- Tissue Inhibitor of Metalloproteinase-2*/genetics
- Tissue Inhibitor of Metalloproteinase-2*/metabolism
- Heart Atria/embryology
- Heart Atria/metabolism
- Heart Ventricles/embryology
- Heart Ventricles/metabolism
- Animals
- Gene Expression Regulation, Developmental
- Biomechanical Phenomena
- Myocardium/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Heart*/embryology
- Myocardial Contraction/physiology
- Zebrafish*/embryology
- Zebrafish*/metabolism
- Extracellular Matrix*/metabolism
- Morphogenesis
- PubMed
- 38984541 Full text @ Development
Citation
Gentile, A., Albu, M., Xu, Y., Mortazavi, N., Ribeiro da Silva, A., Stainier, D.Y.R., Gunawan, F. (2024) Mechanical forces remodel the cardiac extracellular matrix during zebrafish development. Development (Cambridge, England). 151(13):.
Abstract
The cardiac extracellular matrix (cECM) is fundamental for organ morphogenesis and maturation, during which time it undergoes remodeling, yet little is known about whether mechanical forces generated by the heartbeat regulate this remodeling process. Using zebrafish as a model and focusing on stages when cardiac valves and trabeculae form, we found that altering cardiac contraction impairs cECM remodeling. Longitudinal volumetric quantifications in wild-type animals revealed region-specific dynamics: cECM volume decreases in the atrium but not in the ventricle or atrioventricular canal. Reducing cardiac contraction resulted in opposite effects on the ventricular and atrial ECM, whereas increasing the heart rate affected the ventricular ECM but had no effect on the atrial ECM, together indicating that mechanical forces regulate the cECM in a chamber-specific manner. Among the ECM remodelers highly expressed during cardiac morphogenesis, we found one that was upregulated in non-contractile hearts, namely tissue inhibitor of matrix metalloproteinase 2 (timp2). Loss- and gain-of-function analyses of timp2 revealed its crucial role in cECM remodeling. Altogether, our results indicate that mechanical forces control cECM remodeling in part through timp2 downregulation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping