Alterations in the functions of vascular endothelial cells (ECs) induced by fluid shear stress may play a pivotal role in both the development and prevention of vascular diseases. We found that DNA synthesis of bovine aortic and human umbilical vein ECs, determined by [(3)H]thymidine incorporation, was inhibited by steady laminar shear stress (5 and 30 dyne/cm(2)). This growth inhibition due to shear stress was associated with suppression of cell transition from the G(1) to S phase of the cell cycle. Therefore, we studied G(1)-phase events to find the molecules responsible for this cell cycle arrest. Shear stress inhibited the phosphorylation of a retinoblastoma protein (pRb) and the activity of cyclin-dependent kinase (cdk) 2 and cdk4, which phosphorylate pRb. The level of cdk inhibitor p21(Sdi1/Cip1/Waf1) protein, but not that of p27(Kip1), increased as a result of shear stress, and the amount of p21 protein associated with cdk2 also increased, although the protein level of cdk2 was unchanged. Shear stress markedly elevated the mRNA level of p21, and this elevation in mRNA faded after the release of cells from shear stress, concomitant with a recovery of DNA synthesis. These results suggest that steady laminar shear stress induces cell cycle arrest by upregulating p21. Derangement of the steady laminar flow may release cells from this inhibition and induce cell proliferation, which, in turn, may cause atherosclerosis through the induction of EC stability disruption.
Melting of a natural peridotite (spinel‐bearing lherzolite) which occurs as a nodule in the tuff of Salt Lake, Hawaii, has been studied at pressures between 1 atm and 50 kb under anhydrous conditions and at pressures between 20 and 60 kb under hydrous conditions with the tetrahedral‐anvil type of high‐pressure apparatus. Under anhydrous conditions the lherzolite begins to melt near the liquidus of some olivine tholeiites. Garnet is stable near the solidus at pressures higher than at least 30 kb. Under hydrous conditions, when sealed capsules are used, the solidus of the lherzolite is at about 1000°C at 26 kb and about 1150°C at 60 kb. It is 400–700°C lower than the solidus under anhydrous conditions. When unsealed capsules are used, the solidus is raised by 200–400°C from the solidus determined by using sealed capsules. From the present experiments it appears that under anhydrous conditions magmas of olivine tholeiite composition can be formed from lherzolite, but those of quartz‐tholeiite composition cannot be formed by partial melting, at least in the pressure range 10–30 kb. Quartz‐tholeiite magma, however, can be formed within a much larger pressure range under hydrous conditions. The solidus under hydrous conditions (water pressure is equal to total pressure) would give a possible lowest temperature of beginning of melting of the upper mantle. It is also suggested that the partial melting of the hydrous upper mantle may play an important part in the formation of the low‐velocity zone.
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