Microvascular endothelial cells form the semipermeable wall of capillaries and venules that are essential for regulating blood-tissue exchange. Although clinical studies suggest that increased transvascular flux of fluid and proteins in pre-eclampsia might be due to endothelial barrier failure in pre-eclampsia, the molecular mechanisms underlying the pathological regulation of microvascular endothelium remain to be investigated. Transendothelial movement of fluid and solutes is a dynamic process regulated by a complex interaction between signaling molecules and structural elements comprising the cell cytoskeleton, cell-cell adherence, and cell matrix attachment. Further work is required to unravel the intracellular signaling pathways that mediate increased permeability and the molecular events that alter the endothelial barrier structure. There is convincing evidence that pre-eclampsia is an exaggerated inflammatory state, and, as indicated earlier in the chapter, clinical studies have shown a significant correlation between microvascular permeability and levels of TNF-a. Further research is required to investigate the specific intracellular pathways by which inflammatory mediators increase microvascular permeability, particularly the roles of phospholipase C, cyto-solic calcium, protein kinase C, nitric oxide synthase, and guanylate cyclase. More work is also required on how the permeability-inducing signals result in the formation of intercellular gaps through disorganization of junctional proteins and focal adhesion phosphorylation and redistribution, if we are to fully understand the mechanism of enhanced microvascular permeability in pre-eclampsia.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.