The Effect of Pressure on Fluid Transport Across the Endothelial Layer of a Rat Aorta

The research in the Atherosclerosis lab of Professor David Rumschitzki is aiming to understand how Low Density Lipoproteins (LDL) cholesterol penetrate across the endothelial layers of the main large, high pressure arteries (e.g., the aorta), which is thought to be the first step in the processes leading to arterial lesions and eventually to atherosclerosis and heart disease. This research may lead to a potential strategy to slow down lesion formation and, eventually, disease progress. Our laboratory carries out various experiments and simultaneously develops mathematical theory, each of which directs the other, in order to achieve this goal.

My work focuses on the analysis of the thickness of the sub-endothelial intima (SI) layer in a rat aorta that has been fixed under pressure either with or without treatment with a chemical that has been shown to affect the expression of a particular membrane protein. The theory suggests that treatment should result in a thicker SI, which would lead to a larger trans-vessel-wall water flow. This enhanced flow should dilute the lipid (LDL) concentration in the SI and thereby slow down its rate of entrainment in the SI, the earliest step in lesion formation. My independent work begins after the dissection of Sprang Dawley rats whose arteries have been pre-fixed under pressure with or without treatment and the extraction of these rat aortas. I perform the embedding of the rat aorta into a solid block, performing random sectioning of a given embedded aorta sample, staining the acquired sections with Uranyl Acetate and Lead Citrate to introduce contrast to the sample, producing TEM images of the endothelial region of these sections and measuring the thickness of a large number of random sections of the arterial sub-endothelial layer using a program written in MatLab. Theory developed in the group predicts how the level of expression of the membrane protein should affect the thickness of this sub-endothelial layer as a function of pressure and, as noted, how this should affect the rate of lipid entrainment and accumulation in the arterial SI.