About the Project
Endothelial cells constitute the inner layer of the lymphatic and vascular blood vessels, and dysregulation of these cells is implicated in many cardiovascular diseases such as atherosclerosis (6). Panx1 has been shown to be expressed in endothelial cells and is thought to be involved in mediating vascular inflammation during ischaemia (7-8). The functional expression of Panx2, on the other hand, has not been characterised, although a recent paper reported that it is lowly expressed in lymphatic endothelial cells, but did not investigate its function (9).
We have preliminary RNA-seq data on human arterial and venous endothelial cells isolated from human umbilical cords showing that Panx1 and Panx2 are moderately expressed, however, differentially, in both cell types. Whilst the expression of Panx1 was significantly higher in venous endothelial cells, Panx2 was more prominently expressed in arterial endothelial cells. This is interesting as it raises questions about whether the two isoforms serve different or redundant functions. We aim to investigate the following:
1. Characterisation of Panx1 and Panx2 expression in primary arterial and venous endothelial cells via.
2. Exploration of the potential coupling between Panx1 and Panx2 in primary arterial and venous endothelial cells.
3. Investigation of the functional role of Panx2 in primary arterial and venous endothelial cells.
2. Makarenkova H, Shah S and Shestopalov V. The two faces pf pannexins: new roles in inflammation and repair. Journal of Inflammation Research. 2018; 11: 273-288.
3. Le Vasseur M, Lelowski J, Bechberger JF, Sin WC, Naus CC. Pannexin 2 protein expression is not restricted to the CNS. Front Cell Neuroscience. 2014; 8: 392.
4. Iwamoto T, Nakamura T, Doyle A, et al. Pannexin 3 regulates intracellular ATP/cAMP levels and promotes chondrocyte differentiation. Journal of Biological Chemistry. 2010; 285(24): 18948-58.
5. Velasquez S and Eugenin E. Role of Pannxin-1 hemichannels and purinergic receptors in the pathogenesis of human diseases. Frontiers in Physiology. 2014; 5: 1-12.
6. Gimbrone MA and Garcia-Cardena G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circulation Research. 2016; 118 (4): 620-636.
7. Good ME, Eucker SA, Bacon HM, et al. Endothelial cell Pannexin1 modulates severity of ischemic stroke by regulating cerebral inflammation and myogenic tone. The Journal of Clinical Investigation Insight. 2018; 3(6): 1-11.
8. Sharma AK, Charles EJ, Zhao Y, et al. Pannexin-1 channels on endothelial cells mediate vascular inflammation during lung ischemia-reperfusion injury. American Journal of Physiology Lung Cellular and Molecular Physiology. 2018; 315(2): L301-L312.
9. Boucher J, Simonneau C, Denet G, et al. Pannexin-1 in Human Lymphatic Endothelial Cells Regulates Lymphangiogenesis. International Journal of Molecular Sciences. 2018; 19(6): 1558.
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