Spatial relationships in early signaling events of flow-mediated endothelial mechanotransduction.

Blood flow interactions with the vascular endothelium represent a specialized example of mechanical regulation of cell function that has important physiological and pathological cardiovascular consequences. The endothelial monolayer in vivo acts as a signal transduction interface for forces associated with flowing blood (hemodynamic forces) in the acute regulation of artery tone and chronic structural remodeling of arteries, including the pathology of atherosclerosis. Mechanisms related to spatial relationships at the cell surfaces and throughout the cell that influence flow-mediated endothelial mechanotransduction are discussed.

Potential vascular damage from radiation in the space environment.

Cultured endothelial cells of blood vessels have a Do of 2 Gy for X-rays. A dose of 0.5 Gy of X-rays has an acute effect on vessel diameter.

Quantitative studies of endothelial cell adhesion. Directional remodeling of focal adhesion sites in response to flow forces.

Focal adhesion sites were observed in cultured endothelial cells by tandem scanning confocal microscopy and digitized image analysis, techniques that provide real-time images of adhesion site area and topography in living cells. Image subtraction demonstrated that in the presence of unidirectional steady laminar flow (shear stress [tau] = 10 dyn/cm2) a substantial fraction of focal adhesion sites remodeled in the direction of flow. In contrast, focal adhesions of control (no flow) cells remodeled without preferred direction.

Endothelial cell adhesion in real time. Measurements in vitro by tandem scanning confocal image analysis.

Real time measurements of cell-substratum adhesion in endothelial cells were obtained by tandem scanning confocal microscopy of sites of focal contact (focal adhesions) at the abluminal cell surface. Focal contact sites were sharply defined (low radiance levels) in the living cell such that the images could be enhanced, digitized, and isolated from other cellular detail. Sites of focal contact are the principal determinant of cell-substratum adhesion.

Hemodynamic forces and vascular cell communication in arteries.

As the interface between the blood and the rest of the vessel wall, the endothelium is directly affected by hemodynamic shear stress (frictional) forces that locally regulate vascular tone and are implicated in the localization of atherosclerosis. There are many diverse responses of endothelial cells to hemodynamically related mechanical stresses ranging from ion channel activation to gene regulatory events. The processes of force transmission from the blood to the cell, and force transduction within the endothelium to electrophysiologic, biochemical, and transcriptional responses are poorly understood.