Intracellular Calcium Responses of Endothelial Cells Exposed to Pulsatile and Oscillatory Fluid Mechanical Shear Stresses
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Date
2017-05
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The Ohio State University
Abstract
Calcium (Ca2+) is a ubiquitous 2nd messenger that dictates many cellular pathways including muscle contraction, cell proliferation, and apoptosis. Disregulation of Ca2+ homeostasis is believed to contribute to vascular endothelial cell (EC) dysfunction, which transitions the endothelium to a pro-inflammatory mode, initiating atherosclerosis. Since ECs are continually exposed to fluid mechanical shear stress from blood flow, the effect that shear stress has on the intracellular Ca2+ levels ([Ca2+]i) is of major interest. Increases in fluid shear stress are known to increase cytosolic Ca2+. In ECs, the endoplasmic reticulum (ER), the mitochondria, and the extracellular media are the three main sources of Ca2+ attributed to this response. Their relative contribution to the [Ca2+]i response under steady laminar shear stress was investigated previously in our laboratory, but this flow profile is not experienced in human arteries. This study aims to expand upon our earlier published work by investigating the shear-induced [Ca2+]i response of cultured ECs to differing physiological flows, specifically pulsatile (10±5 dyn/cm2) and oscillatory (0.1±5 dyn/cm2) laminar flows. To monitor the Ca2+ response to flow, ECs were incubated with the Ca2+-sensitive probe Fluo-4, and then sheared in the presence of either pulsatile or oscillatory flow. Based on normalized fluorescence responses corresponding to [Ca2+]i responses, oscillatory flow was found to exhibit lower peak magnitudes, higher % of oscillating cells, and no synchronization at shear onset compared to pulsatile flow. This study quantitatively characterized the [Ca2+]i responses under both flow profiles and determined significant differences between them. Further experimentation researching the [Ca2+]i mechanisms responsible for the contrasting [Ca2+]i responses is still needed. A greater understanding of these phenomena could lead to better drug development to prevent and/or treat endothelial dysfunction, and ultimately delay or reverse cardiovascular disease.
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Undergraduate Research Scholarship
Research Scholars Award
Undergraduate Education Summer Research Fellowship
Research Scholars Award
Undergraduate Education Summer Research Fellowship
Keywords
calcium, shear stress, mechanotransduction, pulsatile flow, oscillatory flow