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.
