Biomedical subjects

Ayelet Shay-Salit

Publications and source records attributed to Ayelet Shay-Salit.

4 recordsLinked to original sources

PubMed2003

Transcriptional and post-translation regulation of the Tie1 receptor by fluid shear stress changes in vascular endothelial cells.

The interaction between the vascular endothelium and hemodynamic forces (and more specifically, fluid shear stress), induced by the flow of blood, plays a major role in vascular remodeling and in new blood vessels formation via a process termed arteriogenesis. Tie1 is an orphan tyrosine kinase receptor expressed almost exclusively in endothelial cells and is required for normal vascular development and maintenance. The present study demonstrates that Tie1 expression is rapidly down-regulated in endothelial cells exposed to shear stress, and more so to shear stress changes. This down-regulation is accompanied by a rapid cleavage of Tie1 and binding of the cleaved Tie1 45 kDa endodomain to Tie2. The rapid cleavage of Tie1 is followed by a transcriptional down-regulation in response to shear stress. The activity of the Tie1 promoter is suppressed by shear stress and by tumor necrosis factor alpha. Shear stress-induced transcriptional suppression of Tie1 is mediated by a negative shear stress response element, localized in a region of 250 bp within the promoter. The rapid down-regulation of Tie1 by shear stress changes and its rapid binding to Tie2 may be required for destabilization of endothelial cells in order to initiate the process of vascular restructuring.

Animals↗

PubMed2003

Fluid shear stress and the vascular endothelium: for better and for worse.

As blood flows, the vascular wall is constantly subjected to physical forces, which regulate important physiological blood vessel responses, as well as being implicated in the development of arterial wall pathologies. Changes in blood flow, thus generating altered hemodynamic forces are responsible for acute vessel tone regulation, the development of blood vessel structure during embryogenesis and early growth, as well as chronic remodeling and generation of adult blood vessels. The complex interaction of biomechanical forces, and more specifically shear stress, derived by the flow of blood and the vascular endothelium raise many yet to be answered questions:How are mechanical forces transduced by endothelial cells into a biological response, and is there a "shear stress receptor"?Are "mechanical receptors" and the final signaling pathways they evoke similar to other stimulus-response transduction systems?How do vascular endothelial cells differ in their response to physiological or pathological shear stresses?Can shear stress receptors or shear stress responsive genes serve as novel targets for the design of diagnostic and therapeutic modalities for cardiovascular pathologies?The current review attempts to bring together recent findings on the in vivo and in vitro responses of the vascular endothelium to shear stress and to address some of the questions raised above.

Adaptation, Physiological↗

PubMed2003

Hemodynamic forces as a stimulus for arteriogenesis.

Ischemic heart diseases put a heavy economical burden on Western society. They remain one of the major causes of morbidity, and preventive or postoperative treatments are lengthy and expensive. In some patients of ischemic heart diseases, there is not a direct correlation between the degree of occlusion of major arteries and the development of medical symptoms or damage to the heart function. Interestingly, these patients develop well-formed collateral vessels that compensate for the decrease in blood supply to the heart wall. Clearly, the ability to understand why and how these patients develop collateral vessels may serve as a base for a new strategy to treat ischemic heart diseases by promoting collateral formation. The current article summarizes recent advances in the understanding of how collateral vessels develop and offers the authors' point of view on the central role of biomechanical forces in this process and the molecular mechanisms that underline it.

Animals↗

PubMed2002

VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells.

Blood-flow interactions with the vascular endothelium represents a specialized example of mechanical regulation of cell function that has important physiological and pathophysiological cardiovascular consequences. Yet, the mechanisms of mechanostransduction are not understood fully. This study shows that shear stress induces a rapid induction as well as nuclear translocation of the vascular endothelial growth factor (VEGF) receptor 2 and promotes the binding of the VEGF receptor 2 and the adherens junction molecules, VE-cadherin and beta-catenin, to the endothelial cytoskeleton. These changes are accompanied by the formation of a complex containing the VEGF receptor 2-VE-cadherin-beta-catenin. In endothelial cells lacking VE-cadherin, shear stress did not augment nuclear translocation of the VEGF receptor 2 and phosphorylation of Akt1 and P38 as well as transcriptional induction of a reporter gene regulated by a shear stress-responsive promoter. These results suggest that VEGF receptor 2 and the adherens junction act as shear-stress cotransducers, mediating the transduction of shear-stress signals into vascular endothelial cells.

Active Transport, Cell Nucleus↗