Voelcker Academy

Research Symposium 2012

 

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Jessica Anthony

Ursolic Acid and its Triterpenoid Analogs are Natural Inhibitors of Monocyte Dysfunction

Jessica Anthony

Mentor(s): Jonah Crayton, Sarah Ullevig, and Reto Asmis PhD

Atherosclerosis begins with monocyte migration into the arterial wall. It is characterized by the deposition of lipoproteins and fatty material along the inner walls of these arteries. The monocytes are recruited into the vessel wall by monocyte chemoattractant protein 1 (MCP-1), which leads the cells to the site of inflammation. This ultimately hardens and narrows the arterial walls, which can have fatal consequences. Atherosclerosis can be caused by obesity, genetics, a high fat diet, high cholesterol, high blood pressure, smoking, age, and diabetes. It occurs in various arteries starting from an early age, however, symptoms do not appear until middle-age. Metabolic stress (MS) and Nox4 expression accelerate this chemotaxis of monocytes. Exaggerated monocyte migration can be a harmful event as the monocytes turn into macrophages, take up cholesterol and drive the progression of atherosclerotic lesions.

Previous experiments have shown that in diabetic mice ursolic acid is an inhibitor of monocyte dysfunction and accelerated atherosclerosis. This is where my project comes into play. The results of my project will help us find and develop more powerful analogs of ursolic acid for use as dietary supplements for the prevention accelerated atherosclerosis.

Central Hypothesis: Ursolic acid and its triterpenoid analogs prevent monocyte dysfunction induced by metabolic stress by preventing the induction and overexpression of Nox4.

Specific Aim 1: To test if treatment of THP-1 cells with ursolic acid or its triterpenoid analogs protect against MS induced accelerated chemotaxis.

Specific Aim 2: To test if treatment of THP-1 cells with ursolic acid or its triterpenoid analogs prevent Nox4 overexpression induced by MS.