Relationship between microvascular permeability and ultrastructure

Area of Science:

• Endothelial biology
• Vascular physiology
• Cellular transport

Background:

• The endothelial cell wall forms a critical barrier regulating exchange between blood and tissues.
• Understanding the structure-function relationship of this barrier is key to comprehending vascular permeability.
• Previous research has identified fluid channels but struggled to pinpoint the molecular filter for macromolecules.

Purpose of the Study:

• To review recent advances in understanding the endothelial barrier's structure and function.
• To explore experimental techniques correlating endothelial cell wall structure with barrier function.
• To emphasize the dynamic nature of the endothelial barrier.

Main Methods:

• Review of experimental techniques yielding structure-function correlations.
• Analysis of studies on fluid-conducting channels (clefts, fenestrae, cell junctions).
• Examination of evidence for molecular filters in fenestrated and continuous endothelium.

Main Results:

• Fluid channels are located in clefts, fenestrae, and open cell junctions.
• The molecular filter limiting macromolecular exchange remains challenging to identify.
• Evidence suggests filters may be in fenestral diaphragms, basement membranes, intercellular clefts, or vesicle openings.
• The endothelial cell coat (glycocalyx) significantly retards macromolecular movement.
• Inflammation increases fluid flux via endothelial cell shape modulation and calcium signaling.
• Macromolecular leakage increases with gap formation and glycocalyx modulation.

Conclusions:

• The endothelial barrier's permeability is regulated by dynamic structural and molecular components.
• The glycocalyx plays a crucial role in limiting macromolecular passage.
• Inflammation significantly alters endothelial barrier function through cellular shape changes and glycocalyx modulation.