Peter Oettgen, MD
Director of Preventative Cardiology
Associate Professor of Medicine
Beth Israel Deaconess Medical Center
Harvard Medical School
330 Brookline Avenue, RN 270D
Boston, MA 02215
Dr. Oettgen is the Director of Preventive Cardiology at Beth Israel Deaconess Medical Center in Boston, MA, and an Associate Professor of Medicine at Harvard Medical School. Dr. Oettgen completed his undergraduate training at Bowdoin College in Brunswick, Maine, followed by medical school training at the University of Connecticut. He complete a residency in Internal Medicine at Tufts New England Medical Center, and a Cardiology Fellowship at Beth Israel Hospital in Boston. He has been a member of the faculty at Beth Israel Deaconess Medical Center since 1993. As the Director of Preventive Cardiology, he directs an outpatient prevention program called the Cardiovascular Health and Lipid Clinic where patients with a variety of lipid disorders and hypertension are treated.
Vascular Development and Inflammation
One of the major research focuses in the laboratory is to understand the molecular mechanisms underlying blood vessel development. Although many growth factors and their receptors have been identified that are critical for blood vessel development, much less is known about the transcription factors that regulate this process and may serve as master switches for initiating these events. As an example, we have focused on the transcriptional regulation of the Tie1 and Tie2 genes. These are tyrosine kinases that are required for vascular development. The genomic regulatory elements required for the vascular-specific expression of these genes have been identified but not the transcription factors that are required to express the Tie genes. The ETS factors are a family of highly conserved transcription factors that are involved in regulating development and cellular differentiation. Among the Ets factors, we have identified NERF and ELF-1 as potent transactivator of the Tie genes. We have identified specific binding sites within the regulatory regions of these genes. Using the chicken model of vascular development, we have identified the chicken homologue of the Ets factor ELF-1 as being enriched in developing blood vessels. Thus in addition to their known role in hematopoiesis, our studies demonstrate a dual role for selected members of the Ets factor family such as NERF and ELF-1 in blood vessel development and hematopoiesis. The goals of the future studies will be to identify the role of these factors in regulating endothelial differentiation from pluripotent stem cells, their ability to regulate endothelial function, and identify their role in angiogenesis.
Vascular inflammation is associated with several diseases. The most common disease in the United States is coronary heart disease. The underlying disease process resulting in coronary heart disease is atherosclerosis. This process is initiated when lipid particles containing cholesterol and other fats enter blood vessels where they become modified and lead to an inflammatory response in the blood vessel. This is associated with the induction of a variety of growth factors and matrix degrading enzymes that can eventually lead to a rupture on the inner surface of the blood vessel and lead to a heart attack. Although many of the genes that are activated during vascular inflammation are known, the earliest steps that are required for the initiation of this process are still largely unknown. One of the key regulators for regulating the expression of genes within blood vessels are transcription factors. These factors can serve as master switches for activating whole sets of genes. One of the transcription factors that is known to be activated during vascular inflammation is nuclear factor kappa B(NF-kB). We have identified another transcription factor of the Ets family that is activated in vascular smooth muscle cells and endothelial cells in response to inflammatory stimuli. This factor, ESE-1 is not present in quiescent vascular cells, but is markedly upregulated in response to inflammatory cytokines. We have identified that this factor can interact with the transcription factor NF-kB to regulate the expression of the nitric oxide synthase gene. Nitric oxide synthases make nitric oxide, which is a vasodilator, that is important for normal function of blood vessels. In a mouse model of bacterial sepsis, associated with acute vascular inflammation we found that the expression of ESE-1 was upregulated and correlated with the induction of nitric oxide synthase 2(NOS2) the inducible form of nitric oxide synthase. More recently, we have determined a role for the ETS factor Ets-1 in the regulation of vascular inflammation downstream of PDGF-BB and Angiotensin II. Ets-1 regulates the expression of MCP-1, VCAM-1, and NAD(P)H oxidases, such as p47phox.
New and Noteworthy Publications
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Zhan Y, Brown C, Maynard E, Anshelevich A, Ni W, Ho I, and
Oettgen P. Ets-1 is a critical regulator of angiotensin II mediated vascular inflammation and remodeling. J Clin Invest. 2005 115(9):2508-2516.
This study demonstrates the pivotal role of the ETS transcription factor in the regulation of vascular inflammation and remodeling downstream of Angiotensin II. Target genes downstream of Ets-1 include MCP-1 and VCAM-1.
Huang X, Brown C, Ni W, Maynard E, Rigby AC,
Oettgen P. Critical role for the Ets transcription factor ELF-1 in the development of tumor angiogenesis. 2006; Blood 107:3153-3160.
We have previously demonstrated that the ETS factor ELF-1 is upregulated during vascular development. In this study we similarly demonstrate a role for ELF-1 in the regulation of tumor angiogenesis, and the ability to inhibit tumor angiogenesis using dominant-negative peptides directed against ELF-1.
Oettgen P, Boyle AJ, Schulman SP, Hare JM. Cardiac Stem Cell Therapy. Need for Optimization of Efficacy and Safety Monitoring. Circulation. 2006 Jul 25;114(4):353-8.
This is a review of the current limitations of stem cell therapy in the treatment of cardiac dysfunction.
Oettgen P. Regulation of vascular inflammation and remodeling by ETS factors. Circ Res. 2006 Nov 24;99(11):1159-66.
This study reviews the growing support for the role of selected members of the ETS transcription factor family in the regulation of vascular inflammation.
Ni W, Zhan Y, He H, Maynard E, Balschi JA,
Oettgen P. Ets-1 Is a Critical Transcriptional Regulator of Reactive Oxygen Species and p47phox Gene Expression in Response to Angiotensin II. Circ Res. 2007; 01(10):985-94.
This study demonstrates an important role for Ets-1 in the regulation of ROS generation in response to Angiotensin II by regulating the NAD(P)H oxidase enzyme subunit p47phox.