Endothelial cell transcriptional regulation in vascular disease

Abstract

Glomerulosclerosis and atherosclerosis are vascular diseases for which currently no curative treatments exist. In the kidney filters (glomeruli), small blood vessels mediate blood filtration. In glomerulosclerosis, scar tissue is formed in the glomeruli, culminating in a disturbed blood filtration and kidney function. In atherosclerosis, thickening of the artery wall leads to the occlusion of this artery. Atherosclerosis can lead to myocardial infarction or stroke. Endothelial cells, covered with a protective gel-like layer called the glycocalyx, form the inner layer of blood vessels and are essential for vascular health. Dysfunction of endothelial cells (for example due to diabetes mellitus) is important for the development of glomerulosclerosis and atherosclerosis. However, relatively little is known about which molecular factors are involved in the development of endothelial dysfunction in glomerulosclerosis and atherosclerosis. Therefore, in this research, the role of certain molecular factors in the development of endothelial dysfunction was investigated in pre-clinical models for glomerulosclerosis and atherosclerosis. It appeared that upon kidney damage, the development of glomerulosclerosis was associated with a compromised glycocalyx. However, inhibition and/or stimulation of certain factors that turn on or turn off genes was beneficial for the glycocalyx, the development of glomerulosclerosis and kidney function. One of these factors was found to play a role in the development of endothelial dysfunction in atherosclerosis as well. In this research, it has been shown that certain factors that turn on or turn off genes, are potential new targets for the treatment of endothelial dysfunction in the development of glomerulosclerosis and atherosclerosis.