Atherosclerosis is a vascular disease that leads to the formation of plaques which clog the vessels and impede normal blood flow tissues. It is a leading cause of heart attacks and strokes. Two factors play key roles in the progression of atherosclerosis: inflammation and lipids. The developing plaque is largely comprised of cholesterol deposited by low-density lipoproteins (LDL), however inflammation is what initiates and propagates plaque formation. Two non-LDL lipid-bearing lipoproteins that mediate inflammation are VLDL and HDL. HDL, transport cholesterol away from plaques act as anti-inflammatory agents; VLDL, the primary triglyceride transporting lipoprotein, can induce inflammation and endothelial dysfunction.
Our research is directed at understanding the relationship between lipoproteins and blood vessel disease by studying the inflammatory components of lipoproteins and how they impact the endothelium. In addition to the fatty acids transported in lipoproteins, they also transport oxygenated fatty acids, or oxylipins. Oxylipins come in many chemical variants to produce a complex matrix of pro-inflammatory and anti-inflammatory agents that are delivered to the endothelium by lipoproteins. Understanding how lipoproteins deliver oxylipins to target tissues and what the impact they have on physiology help develop preventive strategies to this common problem. We are currently engaged in clinical trials in subject with various dyslipidemias to determine the role of lipoprotein-oxylipins in inflammation and the early stages of atherosclerosis. We are also engaged in tracer-label studies of the synthesis and clearance of these oxylipins in animal models.
Physiology Core information.
Gregory Shearer, PhD