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| Ashrafi, Kaveh |
| Barber, Diane L |
| Bernstein, Harold S. |
| Black, Brian L |
| Blanc, Paul D |
| Boushey, Homer A |
| Broaddus, V Courtney |
| Brown, James K |
| Caughey, George H |
| Chapman, Harold A |
| Charo, Israel F |
| Chatterjee, Kanu |
| Chuang, Pao-Tien |
| Clyman, Ronald I |
| Conklin, Bruce R |
| Coughlin, Shaun R |
| Derynck, Rik M |
| Dobbs, Leland G |
| Eisner, Mark D |
| Engel, Joanne N |
| Erle, David J |
| Fahy, John Vincent |
| Farese, Robert V |
| Fielding, Christopher J |
| Fielding, Phoebe |
| Fineman, Jeffrey R |
| Glantz, Stanton A |
| Grossman, William |
| Hawgood, Samuel |
| Ingraham, Holly A |
| Jan, Lily Y |
| Kan, Yuet W |
| Kane, John P |
| Kornberg, Thomas B |
| Kurtz, Theodore W |
| Kwok, Pui-Yan |
| Lazarus, Stephen C |
| Malloy, Mary J. |
| Martin, Gail R |
| Matthay, Michael A |
| Mcdonald, Donald M |
| Mikawa, Takashi |
| Minor, Daniel L |
| Mostov, Keith E |
| Nadel, Jay A |
| Ordahl, Charles P |
| Pitas, Robert E |
| Reiter, Jeremy F. |
| Rosen, Steven D |
| Shaw, Robin M. |
| Sheppard, Dean |
| Simpson, Paul C |
| Stainier, Didier Y. R. |
| Wang, Rong |
| Weiner, Orion D |
| Weisgraber, Karl H |
| Weiss, Arthur |
| Weiss, Ethan J |
| Werb, Zena |
| Wiener-Kronish, Jeanine |
| Young, William L |
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CVRI Scientists
Robert E. Pitas, Ph.D.
Professor of Pathology; Senior Investigator, Gladstone Institute of Cardiovascular Disease, Gladstone Institute of Neurological Disease
Research Interests:
Lipoprotein metabolism in vivo and in vitro; role of lipoproteins in the development of atherosclerosis; lipoprotein receptors and atherosclerosis
Summary:
Elevated low density lipoprotein (LDL) cholesterol is the best-known, but not the only, risk factor for heart disease. High levels of lipoprotein(a) [Lp(a)] are also atherogenic. Plasma Lp(a) levels in excess of 30 mg/dl are associated with atherosclerosis and an increased risk of heart attack and stroke. Research into the role of Lp(a) in these pathologies has been hampered by the lack of a suitable animal model with high-level Lp(a) expression.
To address this problem, we developed transgenic mice with high-level expression of Lp(a). In Lp(a), apolipoprotein(a) [apo(a)], a plasminogen-like glycoprotein, is covalently linked to apoB-100, the protein component of LDL. First, we produced mice expressing apo(a) and crossed them with mice expressing human apoB-100. Using an antibody that detects oxidized phospholipids and oxidized phospholipid protein adducts, we made the interesting discovery that Lp(a) in plasma of these mice contained oxidized phospholipids, whereas LDL did not.
Oxidized LDL is thought to contribute to the development of atherosclerosis. LDL that is retained in the artery wall undergoes oxidative modification with resultant detrimental effects. This oxidized LDL apparently is not released or does not accumulate in plasma. Oxidized phospholipids in LDL are partially responsible for the uptake of lipoproteins by cells, which leads to foam-cell formation and the release of cytokines from cells, resulting in monocyte recruitment to the artery wall and in the proliferation of smooth muscle cells.
Our work is focusing on determining if oxidized phospholipids contribute to the atherogenicity of the Lp(a). Our preliminary data suggest that the Lp(a) in these mice are more atherogenic than similar levels of plasma LDL. However, it is not at all clear why plasma Lp(a) contains oxidized phospholipid and LDL does not. What is the source of the oxidized phospholipid? How does it affect the properties of Lp(a)? These new mouse models are currently being used to study these and other questions related to Lp(a), oxidized phospholipid, and atherogenesis.
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