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Flow regulates intercellular communication in HAEC by assembling functional Cx40 and Cx37 gap junctional channels
Eno Essien Ebong1, Sanghee Kim, Natacha DePaola
1Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|December 20, 2005
Summary
Fluid flow significantly increases endothelial gap junctional intercellular communication (GJIC) in human aortic endothelial cells. This response is primarily mediated by connexin 40 (Cx40), highlighting its role in vascular homeostasis.
Area of Science:
- Cardiovascular Biology
- Cellular Physiology
- Molecular Medicine
Background:
- Gap junctions facilitate cell-to-cell communication crucial for vessel wall homeostasis.
- Vascular endothelial gap junction channels are formed by connexin (Cx) proteins Cx37, Cx40, and Cx43.
- Mechanisms regulating connexin expression and channel assembly remain incompletely understood.
Purpose of the Study:
- To investigate the dynamic regulation of endothelial GJIC by fluid flow.
- To determine the role of individual vascular connexins in functional human endothelial gap junctions.
- To elucidate the impact of physiological flow on connexin expression and communication.
Main Methods:
- Human aortic endothelial cells (HAEC) exposed to physiological flow in a parallel-plate chamber.
- Connexin protein expression and localization assessed via immunocytochemistry.
- Functional GJIC evaluated using dye injection and connexin-mimetic peptide inhibitors.
Main Results:
- Baseline GJIC in HAEC was low despite abundant Cx43 and Cx40 expression.
- Fluid flow induced a time-dependent, 7.5-fold increase in GJIC over 24 hours.
- Flow-induced GJIC augmentation was primarily mediated by Cx40, with contributions from Cx37 and Cx43.
Conclusions:
- Fluid flow dynamically and differentially regulates Cx37, Cx40, and Cx43 expression in endothelial cells.
- Cx40 plays a predominant role in flow-mediated enhancement of GJIC.
- This study provides novel insights into the regulation of endothelial communication by mechanical forces.