Showing papers on "Vascular endothelial growth factor B published in 1978"

Localisation and stimulation of prostacyclin production in vascular cells

Abstract: PROSTACYCLIN (PGI2) was reported by Vane and co-workers as a novel short-lived metabolite of prostaglandin endoperoxides (PGG2 and PGH2) which inhibited platelet aggregation1. Subsequent studies have demonstrated that PGI2 is the most potent inhibitor of platelet aggregation so far described, acting by stimulating platelet adenylate cyclase2–4. PGI2 is produced by isolated blood vessel segments5 and is therefore likely to be of great importance in the maintenance of vascular homeostasis. The cellular localisation and regulation of PGI2 synthesis have not previously been established, although it has been proposed that the main source of PGI2 is through pro-aggregatory prostaglandin endoperoxides released from platelets being enzymatically converted to PGI2 by vascular endothelial cells5,6. We show here that pig aortic endothelial cells, but not aortic smooth muscle cells or fibroblasts, synthesise PGI2. This production of PGI2 is stimulated by incubating endothelial cells with PGG2 or with its precursor, arachidonic acid. Furthermore, PGI2 synthesis is powerfully stimulated by cell-free plasma.

Control of proliferation of human vascular endothelial cells. Characterization of the response of human umbilical vein endothelial cells to fibroblast growth factor, epidermal growth factor, and thrombin.

Abstract: Because the response of human endothelial cells to growth factors and conditioning agents has broad implications for our understanding of wound healing angiogenesis, and human atherogenesis, we have investigated the responses of these cells to the fibroblast (FGF) and epidermal growth factors (EGF), as well as to the protease thrombin, which has been previously shown to potentiate the growth response of other cell types of FGF and EGF. Because the vascular endothelial cells that form the inner lining of blood vessels may be expected to be exposed to high thrombin concentrations after trauma or in pathological states associated with thrombosis, they are of particular interest with respect to the physiological role of this protease in potentiating cell proliferation. Our results indicate that human vascular endothelial cells respond poorly to either FGF or thrombin alone. In contrast, when cells are maintained in the presence of thrombin, their proliferative response to FGF is greatly increased even in cultures seeded at a density as low as 3 cells/mm2. Human vascular endothelial cells also respond to EGF and thrombin, although their rate of proliferation is much slower than when maintained with FGF and thrombin. In contrast, bovine vascular endothelial cells derived from vascular territories as diverse as the bovine heart, aortic arch, and umbilical vein respond maximally to FGF alone and neither respond to nor bind EGF. Furthermore, the response of bovine vascular endothelial cells to FGF was not potentiated by thrombin, indicating that the set of factors controlling the proliferation of vascular endothelial cells could be species-dependent. The requirement of cultured human vascular endothelial cells for thrombin could explain why the human cells, in contrast to bovine endothelial cells, are so difficult to maintain in tissue culture. Our results demonstrate that by using FGF and thrombin one can develop cultures of human vascular endothelial cells capable of being passage repeatedly while maintaining a high mitotic index. The stock cultures used for these studies have been passed weekly with a split ratio of 1 to 10 and are currently in their 30th passage. These cultures are indistinguishable from earlier passages when examined for the presence of Weibel-Palade bodies or Factor VIII antigen. We conclude that the use of FGF and thrombin can prevent the precocious senescence observed in most human endothelial cells cultures previously described.