As the inner lining of the vessel wall, vascular endothelial cells are poised to act as a signal transduction interface between haemodynamic forces and the underlying vascular smooth-muscle cells. Detailed analyses of fluid mechanics in atherosclerosis-susceptible regions of the vasculature reveal a strong correlation between endothelial cell dysfunction and areas of low mean shear stress and oscillatory flow with flow recirculation. Conversely, steady shear stress stimulates cellular responses that are essential for endothelial cell function and are atheroprotective. The molecular basis of shear-induced mechanochemical signal transduction and the endothelium's ability to discriminate between flow profiles remains largely unclear. Given that fluid shear stress does not involve a traditional receptor/ligand interaction, identification of the molecule(s) responsible for sensing fluid flow and mechanical force discrimination has been difficult. This review will provide an overview of the haemodynamic forces experienced by the vascular endothelium and its role in localizing atherosclerotic lesions within specific regions of the vasculature. Also reviewed are several recent lines of evidence suggesting that both changes in membrane microviscosity linked to heterotrimeric G proteins, and the transmission of tension across the cell membrane to the cell-cell junction where known shear-sensitive proteins are localized, may serve as the primary force-sensing elements of the cell.

Background —The effect of temporal and spatial gradients in shear on primary human endothelial cell (HUVEC) proliferation was investigated. The sudden-expansion flow chamber (SEFC) model was used to differentiate the effect of temporal gradients in shear from that of spatial gradients. With a sudden onset of flow, cells are exposed to both temporal and spatial gradients of shear. The temporal gradients can be eliminated by slowly ramping up the flow. Methods and Results —HUVEC proliferation in the SEFC remained unstimulated when the onset of flow was slowly ramped. Sudden onset of flow stimulated a 105% increase of HUVEC proliferation (relative to ramped onset) within the region of flow reattachment. To further separate temporal and spatial gradients, a conventional parallel-plate flow chamber was used. A single 0.5-second impulse of 10 dyne/cm 2 increased HUVEC proliferation 54±3% relative to control. When flow was slowly ramped over 30 seconds, HUVEC proliferation was not significantly different from controls. Steady laminar shear over 20 minutes inhibited HUVEC proliferation relative to controls regardless of step (36±8%) or ramp (21±5%) onsets of flow. Conclusions —The results indicate that temporal gradients in shear stress stimulate endothelial cell proliferation, whereas spatial gradients affect endothelial proliferation no differently than steady uniform shear stress.

We present an overview of the National Science Foundation’s Daniel K. Inouye Solar Telescope (DKIST), its instruments, and support facilities. The 4 m aperture DKIST provides the highest-resolution observations of the Sun ever achieved. The large aperture of DKIST combined with state-of-the-art instrumentation provide the sensitivity to measure the vector magnetic field in the chromosphere and in the faint corona, i.e. for the first time with DKIST we will be able to measure and study the most important free-energy source in the outer solar atmosphere – the coronal magnetic field. Over its operational lifetime DKIST will advance our knowledge of fundamental astronomical processes, including highly dynamic solar eruptions that are at the source of space-weather events that impact our technological society. Design and construction of DKIST took over two decades. DKIST implements a fast (f/2), off-axis Gregorian optical design. The maximum available field-of-view is 5 arcmin. A complex thermal-control system was implemented in order to remove at prime focus the majority of the 13 kW collected by the primary mirror and to keep optical surfaces and structures at ambient temperature, thus avoiding self-induced local seeing. A high-order adaptive-optics system with 1600 actuators corrects atmospheric seeing enabling diffraction limited imaging and spectroscopy. Five instruments, four of which are polarimeters, provide powerful diagnostic capability over a broad wavelength range covering the visible, near-infrared, and mid-infrared spectrum. New polarization-calibration strategies were developed to achieve the stringent polarization accuracy requirement of 5×10−4. Instruments can be combined and operated simultaneously in order to obtain a maximum of observational information. Observing time on DKIST is allocated through an open, merit-based proposal process. DKIST will be operated primarily in “service mode” and is expected to on average produce 3 PB of raw data per year. A newly developed data center located at the NSO Headquarters in Boulder will initially serve fully calibrated data to the international users community. Higher-level data products, such as physical parameters obtained from inversions of spectro-polarimetric data will be added as resources allow.

Objective-In response to changes in wall shear stress (WSS) the vascular endothelium releases several factors, among others nitric oxide. On the basis of studies of endothelial cells in culture, suggesting that platelet endothelial cell adhesion molecule-1 (PECAM-1) is specifically involved in sensing and coupling high temporal gradients of fluid shear stress with activation of eNOS, we hypothesized that dilations of isolated skeletal muscle arterioles from PECAM-1 knockout mice (PECAM-KO) will be reduced to rapid increases in WSS elicited by increases in perfusate flow. Methods and Results-Small and large step increases in flow resulted in substantial dilations in arterioles of WT mice (45Ϯ4%), but they were markedly reduced in arterioles of PECAM-KO mice (22Ϯ5%). The initial slope of dilations, when WSS increased rapidly, was greater in vessels of WT than those of PECAM-KO mice (slopes: 0.378 and 0.094, respectively), whereas the second phase of dilations, when flow/shear stress was steady, was similar in the 2 groups (slopes: 0.085 and 0.094, respectively). Inhibition of eNOS significantly reduced the initial phase of dilations in arterioles from WT, but not from those of PECAM-KO mice. The calcium ionophore A23187 elicited similar NO-mediated dilation in both WT and PECAM-KO mice. Conclusions-In isolated arterioles of PECAM-KO mice activation of eNOS and consequent dilation by agonists is maintained, but the dilation to high temporal gradients of wall shear stress elicited by increases in perfusate flow is reduced. Thus, we propose that PECAM-1 plays an important role in the ability of the endothelium to sense and couple high temporal gradients of wall shear stress to NO-mediated arteriolar dilation during sudden changes in blood flow in vivo. Key Words: PECAM-1 Ⅲ arteriole Ⅲ endothelium Ⅲ flow-induced dilation Ⅲ nitric oxide T he vascular endothelium is uniquely situated to act as the signal transduction interface between hemodynamic forces and the underlying vascular smooth muscle. Increases in shear stress have long been shown to result in vasodilatation mediated, in part, by the endothelium-dependent release of nitric oxide (NO). 1-5 Since endothelium-derived NO was first identified and characterized, fluid shear stress has been established as the most potent stimulus that regulates the activity of endothelial NO synthase (eNOS). 6 We have shown previously that stepwise increases in perfusate flow, via increases in wall shear stress, elicit substantial dilations of isolated arterioles. [3][4][5] Recent in vitro studies in cultured endothelial cells showed that the sudden onset of fluid flow induces a burst of NO production, which seemed to be related more to the magnitude of temporal gradient of shear stress than to its absolute value, 6,7 suggesting that the vascular endothelium is able to discriminate between temporal gradients of shear stress as also proposed by others.7a The molecular basis of shear stress-induced mechanochemical signal transduction, and the endothelium's ability to discriminate betw...