Investigation of Calcium influx in endothelial cells under flow. (360G-Wellcome-202156_Z_16_Z)

Endothelial cell (EC) function is affected by forces generated by flowing blood on the artery wall (wall shear stress, WSS). Unidirectional WSS occurs in unbranched areas of the arteries, which are protected from atherosclerosis, while oscillatory WSS occurs at branch points, where the majority of atherosclerotic plaques are found. ECs can sense force via multiple mechanoreceptors, which induce calcium signalling in response to WSS. Although ECs can distinguish between unidirectional and oscillatory WSS, the mechanisms that control this are unknown. This projects aims to determine the origin of Calcium signalling, which is recorded as a response of endothelial cells to the applied flow. Ca2+ signalling originates either from Ca2+ influx from the media into the cell or from Ca2+ release from the intracellular stores of the endoplasmic reticulum. To discriminate between these two sources, it will be compared flow- induced Ca2+ mechanoresponse in Ca-containing and Ca-free media under unidirectional and 1 Hz oscillatory flow. If the Ca2+ originates from the media, then the cell response/ Ca2+ influx should be decreased in Ca-free conditions. On the other hand, if the Ca2+ is released from intracellular stores, then the response should insensitive to the Ca levels in the media.