Research Summary
Molecular and immunologic determinants of the factors causing atherosclerosis and cardiovascular disease

Our laboratory has a longstanding interest in two major areas. One is the cell biology of the assembly and secretion of the macromolecular complexes that transport lipids (mainly triglycerides and cholesterol) made in the liver to other tissues, where they are used for a number of essential purposes. Some of the strongest risk factors for cardiovascular disease—the leading killer not just in the U.S., but worldwide—are related to the levels of certain lipoproteins in the blood. Thus, information about the mechanisms on how they are formed is of great value in understanding how to regulate the levels of the cardiovascular disease-causing lipoproteins. Recently, we have discovered factors that coregulate lipoprotein assembly and secretion and the formation of the types of lipid droplets that can accumulate to cause “fatty liver”, a serious and increasingly common health problem associated with obesity.

The other major research area is the underlying cause of cardiovascular disease, namely atherosclerosis, the buildup of cholesterol-filled cells that form plaques, such as in the coronary arteries. These plaques can rupture and cause a heart attack. We have pioneered mouse models of atherosclerosis and molecular approaches so that we can discover the key factors that will return a diseased artery back to a healthier state. We have discovered that reducing the levels in the blood of certain lipoproteins coupled with resolving the inflammation of the immune cells in the plaques is the optimal combination to achieve this. We are extending these studies to the molecular level to identify specific therapeutic targets as well as to human plaques and to clinically relevant conditions known to increase plaque inflammation and the risk of cardiovascular disease, such as obesity, insulin resistance, and diabetes.