Vascular permeability modulation at the cell, microvessel, or whole organ level: towards closing gaps in our knowledge

• Published in: Cardiovascular research Vol. 87; no. 2; pp. 218 - 229
• Main Authors: Curry, Fitz-Roy E., Adamson, Roger H.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.07.2010
• Subjects: Animals; Biological and medical sciences; Body Fluids - metabolism; Capillary Permeability; Cardiology. Vascular system; Edema - metabolism; Edema - physiopathology; Endothelial cell heterogeneity; Endothelial glycocalyx; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Glycocalyx - metabolism; Glycocalyx volume; Humans; Inflammation - metabolism; Inflammation - physiopathology; Inflammation Mediators - metabolism; Medical sciences; Mice; Microvessels - immunology; Microvessels - metabolism; Microvessels - physiopathology; Models, Animal; Models, Cardiovascular; Osmotic Pressure; Perfusion and permeability; Rac1 and endothelial permeability; Regional Blood Flow; Spotlight Reviews; Thrombin; Thrombin - metabolism; VE-cadherin and inflammation; Wound healing; Endothelial cell; VE-cadherin and inflammation; Thrombin; Knowledge; Phlebology; Wound; Heterogeneity; Healing agent; Modulation; Blood vessel; Endothelial cell heterogeneity; Cardiology; Cicatrization; Endothelial glycocalyx; Wound healing; Serine endopeptidases; Enzyme; Cell adhesion molecule; Inflammation; Permeability; Cadherin; Perfusion and permeability; Peptidases; Glycocalyx volume; Perfusion; Volume; Hydrolases; Rac1 and endothelial permeability; Level; Circulatory system; Organ
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvq115

Multiple processes modulate net blood-to-tissue exchange in a microvascular unit in normal and pathophysiological conditions. These include mechanisms that control the number and type of microvessels perfused, the balance of adhesion and contractile forces that determine the conductance of the spaces between endothelial cells to water and solutes, the pressure and chemical potential gradients determining the driving forces through these conductive pathways, and the organization of barriers to macromolecules in the endothelial glycocalyx. Powerful methods are available to investigate these mechanisms at the levels of cultured endothelial monolayers, isolated microvessels, and the microvascular units within intact organs. Here we focus on current problems that limit the integration of our knowledge of mechanisms investigated in detail at the cellular level into a more complete understanding of modulation of blood-to-tissue exchange in whole organs when the endothelial barrier is exposed to acute and more long-term inflammatory conditions. First, we review updated methods, applicable in mouse models of vascular permeability regulation, to investigate both acute and long-term changes in permeability. Methods to distinguish tracer accumulation due to change in perfusion from real increases in extravascular accumulation are emphasized. The second part of the review compares normal and increased permeability in individually perfused venular microvessels and endothelial cell monolayers. The heterogeneity of endothelial cell phenotypes in the baseline state and after exposure to injury and inflammatory conditions is emphasized. Lastly, we review new approaches to investigation of the glycocalyx barrier properties in cultured endothelial monolayers and in whole-body investigations.