On-Chip Endothelial Inflammatory Phenotyping

Atherogenesis is potentiated by metabolic abnormalities that contribute to a heightened state of systemic inflammation resulting in endothelial dysfunction. However, early functional changes in endothelium that signify an individual''s level of risk are not directly assessed clinically to help guide therapeutic strategy. Moreover, the regulation of inflammation by local hemodynamics contributes to the non-random spatial distribution of atherosclerosis, but the mechanisms are difficult to delineate in vivo. We describe a lab-on-a-chip based approach to quantitatively assay metabolic perturbation of inflammatory events in human endothelial cells (EC) and monocytes under precise flow conditions. Standard methods of soft lithography are used to microfabricate vascular mimetic microfluidic chambers (VMMC), which are bound directly to cultured EC monolayers.¹ These devices have the advantage of using small volumes of reagents while providing a platform for directly imaging the inflammatory events at the membrane of EC exposed to a well-defined shear field. We have successfully applied these devices to investigate cytokine-,² lipid-^{3, 4} and RAGE-induced⁵ inflammation in human aortic EC (HAEC). Here we document the use of the VMMC to assay monocytic cell (THP-1) rolling and arrest on HAEC monolayers that are conditioned under differential shear characteristics and activated by the inflammatory cytokine TNF-α. Studies such as these are providing mechanistic insight into atherosusceptibility under metabolic risk factors.     

Variability in several ecologic-physiologic traits of different populations of the Asiatic Arctic suslik Citellus parryi]

In several geographic populations of the Arctic ground squirrel C. parryi, studies have been made on changes in oxygen consumption during decrease of the ambient temperature from 25 to 3-4 degrees, thermal preference, hemoglobin content of the blood and composition of the adipose tissue (both brown and white, subcutaneous and visceral). Significant shifts of these indices were found. In animals from various parts of the species area, different sensitivity to cooling was found, as indicated by determinations of oxygen consumption at different temperatures and the prefered temperature: different hemoglobin content of the blood was also found together with differences in the level of two unsaturated fatty acids - the oleic and linoleic ones. Comparison of these data with similar results obtained on various populations of the Siberian ground squirrel C. undulatus revealed obvious differences between these close species with respect to the indices studied.