Vascular permeability factor/vascular endothelial growth factor, XXXX , and @entity7499 .

@entity455 @entity7499 @entity1569 @entity7 @entity5 @entity7790 @entity11924
@entity7 / @entity7 is a multifunctional cytokine that contributes to @entity7499 by both direct and indirect mechanisms. On the one hand, @entity7 / @entity7 stimulates the ECs lining nearby microvessels to proliferate, to migrate, and to alter their pattern of gene expression. On the other hand, @entity7 / @entity7 renders these same microvascular ECs hyperpermeable so that they spill plasma proteins into the extravascular space, leading to the clotting of extravasated fibrinogen with deposition of a fibrin gel. Extravascular fibrin serves as a provisional matrix that favors and supports the ingrowth of new blood vessels and other mesenchymal cells that generate mature, vascularized stroma. These same principles apply in @entity5 , in several examples of non-neoplastic pathology, and in physiological processes that involve @entity7499 and new stroma generation. In all of these examples, @entity11924 and the introduction of a provisional, plasma-derived matrix precede and accompany the onset of EC division and new blood vessel formation. It would seem, therefore, that @entity5 have "borrowed" fundamental mechanisms that developed in multicellular organisms for purposes of tissue defense, renewal, and repair. @entity7 / @entity7 , therefore has taught us something new about @entity7499 ; namely, that @entity455 and consequent plasma protein extravasation are important, perhaps essential, elements in its generation. However, this finding raises a paradox. While @entity7 / @entity7 induces @entity455 , other potent angiogenic factors apparently do not, at least in subtoxic concentrations that are more than sufficient to induce @entity7499 . Nonetheless, wherever @entity7499 has been studied, the newly generated vessels have been found to be hyperpermeable. How, therefore, do angiogenic factors other than @entity7 / @entity7 lead to the formation of new and leaky blood vessels? We do not as yet have a complete answer to this question. One possibility is that at least some angiogenic factors mediate their effect by inducing or stimulating the expression of @entity7 / @entity7 . In fact, there is already one clear example of this. @entity7790 is a potent angiogenic factor but does not itself increase microvascular permeability. However, @entity7790 strikingly upregulates @entity7 / @entity7 expression in cultured keratinocytes and is thought to be responsible, at least in part, for the overexpression of @entity7 / @entity7 in @entity1569 . Moreover, overexpression of @entity7790 , along with that of the EGF receptor with which it interacts, is characteristic of many @entity5 , raising the possibility that @entity7790 acts to stimulate @entity7 / @entity7 expression in other types of epithelial cells and in this manner induces @entity7499 .(ABSTRACT TRUNCATED AT 400 WORDS)
