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Updated: Jan 22, 2026
09:20
Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption
Published on: October 4, 2019
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Cardiomyocyte-myofibroblast contact dynamism is modulated by connexin-43
Francisca Schultz1, Pamela Swiatlowska1, Anita Alvarez-Laviada1
1National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Summary
Cardiomyocyte-myofibroblast contacts are dynamic due to myofibroblast edge movements. Connexin-43 (Cx43) levels and function influence this dynamism, offering a target for treating infarct border zones.
Area of Science:
- Cardiovascular Biology
- Cellular Biophysics
- Tissue Engineering
Background:
- Cardiomyocytes and myofibroblasts interact in infarcted hearts.
- Cellular coupling is crucial, but physical contact dynamics are unquantified.
- Connexin-43 (Cx43) mediates gap junction communication.
Purpose of the Study:
- Quantify the physical dynamics of cardiomyocyte-myofibroblast contacts.
- Investigate the role of connexin-43 (Cx43) in modulating these interactions.
- Explore therapeutic potential for infarct border zone remodeling.
Main Methods:
- Scanning ion conductance microscopy (SICM) to visualize cell-cell contacts.
- Cx43 manipulation (silencing, trafficking inhibition, internalization).
- Pharmacological agents (4-phenylbutyrate, latrunculin-B) and hypoxia.
- Fluorescent dye transfer assays for functional coupling.
Main Results:
- Cardiomyocyte-myofibroblast contacts are highly dynamic, driven by myofibroblast lamellipodia.
- Reduced Cx43 levels or function attenuated contact dynamism.
- Enhanced Cx43 coupling with 4-phenylbutyrate stabilized contacts and increased functional coupling.
- Latrunculin-B decreased dynamism and Cx43 intensity at contacts.
Conclusions:
- Heterocellular cardiomyocyte-myofibroblast contacts are dynamic and influenced by Cx43.
- Cx43 modulation affects both physical contact dynamics and functional coupling.
- Targeting Cx43 may offer a strategy to manage aberrant coupling and myofibroblast proliferation in the infarct border zone.
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