Atherosclerosis, the leading cause of heart disease in developed nations, is an inflammatory disease marked by accumulation of monocytes and macrophages within the walls of arteries. Patients with severe cases of atheroscelosis exhibit elevated levels of blood lipids such as triglyceride-rich lipoproteins (TGRL). There is evidence that TGRL can induce blood vessel endothelial cells to upregulate inflammatory genes and express adhesion molecules that recruit monocytes.

Lipoproteins derived from human blood (green) bind to the surface of arterial endothelial cells

Our lab investigates how unhealthy dietary fats influence vascular inflammation and recruitment of monocytes to the arterial wall. We mimic the influence of a high-fat diet on arterial endothelium by repetitively exposing aortic endothelium in culture to TGRL that is freshly-isolated from human plasma. We have found that TGRL does not directly cause inflammation of the endothelium, but greatly enhances the inflammatory response to injury. We seek to address unanswered questions regarding the early stages of atherosclerosis by:

• Developing vascular-mimetic microfluidic channels (VMMC) to function as a diagnostic tool for assessing the affects of TGRL on recruitment of blood monocytes.

• Determining how blood lipoproteins such as TRGL interact with the endothelium, and through which signaling pathways they enhance inflammation

• Elucidating the adhesion molecules and chemokines that support monocyte arrest and thereby establishing therapeutic targets to antagonize atherogenesis.