Robert E. Pitas, Ph.D.
Senior Investigator
Gladstone Institute of Cardiovascular Disease
Professor of Pathology
University of California, San Francisco
Email: rpitas@gladstone.ucsf.edu
Telephone: 415-734-2000
Fax: 415-355-0824

Areas of Investigation
My research focuses on identifying factors that contribute to the deposition of fat in cells of the artery walls, which eventually leads to the development of atherosclerosis, narrowing of the lumen of the arteries, and heart attack. Whereas many factors contribute to heart disease, our interest is primarily in the contribution of lipoproteins and their receptor to the development of the disease.

Significance
Heart attack is the leading cause of death in the United States. Our work is designed to understand the mechanisms that contribute to the development of heart disease. Understanding the development of the disease will eventually lead to rational strategies for therapeutic intervention.

Approaches
My laboratory studies mechanisms related to the progression and regression of atherosclerotic lesions. We are particularly interested in lipoprotein (a), a lipoprotein that is comprised of apolipoprotein (apo) (a) and low density lipoproteins (LDL), which contain apoB. LDL plays a central role in lipoprotein metabolism and atherosclerosis. Elevated levels of Lp(a) are also associated with increased risk of developing the disease.

It has been hypothesized that these lipoproteins are retained in the artery walls and are oxidized to a form that is internalized by scavenger receptors, which are expressed by macrophages and smooth muscle cells. Scavenger receptors may contribute to atherosclerosis by mediating the accumulation of lipoprotein-derived cholesterol in cells, leading to the accumulation of cholesterol esters and the formation of foam cells. The expression of apoE by macrophages of the arterial wall inhibits the development of atherosclerosis; however, the mechanism for the beneficial effect is not known.
We want to understand how apoB-containing lipoproteins initiate atherosclerosis, how scavenger receptors contribute to the process, and how apoE inhibits the development of atherosclerotic lesions. Each of these areas provides a potential opportunity to develop new therapies for the treatment and prevention of coronary artery disease.

Contributions
Previous work has focused on scavenger receptors and apoE. We discovered that class A scavenger receptors are expressed by human smooth muscle cells and have characterized the regulation of receptor expression in these cells. In addition, we have shown that Nexin II, a protease inhibitor, is a ligand for the scavenger receptor raising the possibility that a balance between scavenger receptor activity and Nexin II might affect proteolytic enzyme activity in atherosclerotic lesions. We have recently shown that the class A scavenger receptor mediates the adhesion of macrophages to extracellular matrix. We have shown that low levels of macrophage-produced apoE reduces the development of atherosclerosis even in the presence of hypercholesterolemia and that the two isoforms of apoE, apoE3 and apoE4, exert different effects on HDL metabolism.

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