Atherosclerosis is the buildup of fatty plaques in the walls of arteries. The disease can lead to heart attacks, strokes, and other major health problems; in fact, atherosclerosis is the most common underlying cause of death in the developed world. It has also been called a “silent killer” because symptoms are not usually apparent until after the disease is significantly advanced. Therefore, it is vital to understand the process of atherosclerosis development and progression to predict and prevent the adverse health issues caused by the disease.
Previous research has shown that certain locations in the arteries are more susceptible to atherosclerosis than others. This is partly due to the effect of mechanical forces on endothelial cells, which line the inside of arteries and veins. These cells are sensitive to forces like fluid shear stress (caused by blood flow) and cyclic circumferential stretch (caused by the artery stretching as the heart beats). Endothelial cells respond to these forces by changing their orientation, structure, protein expression, etc., which can make the arteries more vulnerable to atherosclerosis. In an ideal, straight artery, shear stress and stretch are acting in perpendicular directions. However, in areas susceptible to the disease (i.e., the carotid bifurcation), there tend to be helical flow patterns such that the direction of the flow and the stretch on the cells is closer to parallel. To our knowledge, no one has studied the effects of this change in relative direction between shear stress and stretch on the endothelial cells.
For this project, our lab has developed an in vitro cell culture system (the “Stress Angle Device”) capable of applying simultaneous fluid shear stress and cyclic circumferential stress to cultured endothelial cells. Using this device, we are able to alter the relative orientation of the shear stress and stretch (i.e., the “stress angle”) on the cultured cells. This allows us to reproduce the mechanical environment experienced by cells in locations susceptible to atherosclerosis. Then, we investigate cell response to these conditions through imaging and biochemical techniques to study the mechanical risk factors and the progression of atherosclerosis.