Molecular Mechanisms of Endothelial Hyperpermeability

Vascular permeability reflects changes in the function of the endothelium, its interendothelial junctions and transcellular delivery. Here, we show that common molecular mechanisms exist between VEGF and histamine in regulating vascular hyperpermeability. Crosstalk between downstream signaling of VEGF and histamine receptors are involved in calcium signaling and cell proliferation. Understanding the molecular mechanisms of vascular permeability is crucial in order to reduce vascular hyperpermeability and oedema in various pathological conditions and in VEGF therapy. Overall design: In despite of the substantial knowledge of VEGF and histamine signal transduction and their physiological responses, molecular mechanisms inducing endothelial cell permeability and proliferation have remained inconclusive. To monitor the transcriptional alteration of proteins known to regulate the endothelial permeability, next-generation RNA sequencing was used. Fold changes of several genes known to regulate calcium signaling, cell adhesion, cell proliferation, ion flux and immune response were compared between the permeabilizing agents.

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Laakkonen JP, Lappalainen JP, Theelen TL, Toivanen PI, Nieminen T, Jauhiainen S, Kaikkonen MU, Sluimer JC, Ylä-Herttuala S