Abstract
A common end point of many signaling pathways to increase permeability in cultured endothelial cell monolayers is increased phosphorylation of myosin light chains, a step assumed to be necessary for activation of contractile mechanisms in endothelial cells. However, the signaling pathways which modulate permeability in cultured endothelial cells, differ significantly from those that regulate permeability in intact venular microvessels. One reason for this difference may be that endothelial cells in culture express a phenotype with exaggerated contractile machinery. If this phenotype arises as the result of the process of harvesting and culturing endothelial cells, it is possible that some endothelial cells in culture are more characteristic of microvessel endothelium that has been subjected to injury (e.g. from oxidant stress, leukocyte attachment, or repeated expsoure to inflammatory conditions) than the endothelium of uninjured microvessels. It follows that agents that attenuate increased endothelial barrier permeability in cultured endothelial monolayers (e.g. regulators of the Rho-Rho kinase pathway, including the statins) may be useful candidates for the treatment of chronic dysfunction of the endothelial barrier.
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Supported by NIH grants R37HL28607 and RO1HL 44485.
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Curry, FR.E. Microvascular injury: Mechanisms and modulation. International Journal of Angiology 11, 1–6 (2002). https://doi.org/10.1007/s00547-001-0044-x
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DOI: https://doi.org/10.1007/s00547-001-0044-x