Burton E. Sobel, MD, FACC, FACP (Master), FAHA

Education:

Training:

Residency

Fellowship

Specialty:

Certifications:

Academic Appointments:

Biography:

Dr. Sobel is Director of the Cardiovascular Research Institute at the University of Vermont. Dr. Sobel has served on countless professional societies and editorial boards, is presently President of the Society for Experimental Biology and Medicine, and has been repeatedly honored by a variety of professional and business groups, including several awards from the American Heart Association. He was also given a Research Career Development Award from the NIH, Distinguished Scientist Award, from the American College of Cardiology, a Distinguished Achievement Award from the AHA and the ACC, an International Recognition Award from the Heart Research Foundation, and a Mastership from the American College of Physicians. Dr. Sobel has lectured and published widely, served as a consultant on many corporate boards, holds several patents, and has a particular research interest in the connection between diabetes and heart disease. He and his wife, Susan, a family therapist, live in Colchester and have two grown children.

Major Research Interests:

Developed and validated methods by which biochemical quantification of the extent of myocardial infarction could be accomplished in vivo based on sequential analyses of concentration in plasma of macromolecules (CK, MB CK isoenzymes, and other moieties) and applied them to determine whether the extent of infarction was an important determinant of prognosis after myocardial infarction and furthermore, whether the extent of infarction could be modified by interventions that reduce myocardial oxygen requirements or increase myocardial oxygen supply.  This work has had a major impact on how patients with acute myocardial infarction are treated and led to a reduction of mortality secondary to treatments, such as thrombolysis, that were validated initially with the methods developed;

Contributed to the initial development of cardiac positron emission tomography with the use of positron-emitting radionuclides including carbon-11 labeled palmitate, the physiological fuel of myocardium, and applied it to further delineate the nature of evolution of infarction and its interdiction with interventions salvaging ischemic myocardium including coronary thrombolysis with clot-selective fibrinolytic agents;

Pioneered coronary thrombolysis with the use of the clot-selective plasminogen activator, tissue-type plasminogen activator (t-PA), in studies of cells in culture, experimental animals, and mechanistic clinical studies in patients with acute myocardial infarction with quantification of the extent of infarction by positron emission tomography and analysis of time activity curves in blood of enzymes liberated from myocardium.  This work provided a foundation for subsequent large-scale, multicenter clinical trials in which Dr. Sobel played a leadership role that demonstrated the efficacy of coronary thrombolysis with clot-selective agents, heparin, and aspirin in the reduction of death associated with coronary artery disease and acute myocardial infarction;

Recently delineated altered fibrinolysis in blood and myocardium and altered proteolytic activity in vessel walls as mediators of deleterious effects of hyperinsulinemia associated with insulin resistance, impaired glucose tolerance, and type 2 diabetes thereby helping to elucidate the pathophysiology of macrovascular angiopathy and heart failure in type 2 diabetes.  This work, coupled with results of studies demonstrating that insulin sensitizers normalize fibrinolysis in patients with type 2 diabetes, is changing the approach to their treatment directed at reducing the risk of heart attack and cardiac death.

Recent Grant Support

Grant Title: Hemostasis & Thrombosis Program for Trainees
Sponsor: National Institutes of Health
Co-Investigator: Dr. Burton E. Sobel; Dr. Kenneth G. Mann (PI)

Grant Title: Postdoctoral Cardiovascular Research Training Program
Sponsor: National Institutes of Health
Co-Investigator: Dr. Burton E. Sobel; Dr. Martin M. LeWinter (PI)

Grant Title: Reduction of infarct size by administration of erythropoietin, an anti-injury agent.
Sponsor: H.H. Sheikh Hamdan Award (UAE)
Principal Investigator: Dr. Burton E. Sobel

Grant Title: Translational Research in Lung Biology and Disease
Sponsor: National Institutes of Health
Co-Investigator: Dr. Burton E. Sobel; Dr. Charles G. Irvin (PI)

Grant Title: BARI 2D – Fibrinolysis and Coagulation Core
Sponsor: National Institutes of Health
Principal Investigator:  Dr. Burton E. Sobel

Grant Title: The Medtronic, Inc. / Cardiovascular Research Institute Distinguished Research  Center (DRC)
Sponsor: Medtronic, Inc.
Principal Investigator: Dr. Burton E. Sobel

Grant Title: New England, New York, and Quebec Regional Clinical Center
Sponsor: National Institutes of Health
 Co-Principal Investigator: Dr. Burton E. Sobel; Dr. Martin M. LeWinter (PI)

Grant Title:  Elucidating the Functional Significance of Increased Plasminogen Activator Inhibitor type-1 (PAI-1) in the Heart and Its Modulation with Transcription Activation Technology
Sponsor:  Intrexon, Inc.
Principal Investigator:  Dr. Burton E. Sobel

Grant Title:  The Takeda Pharmaceutials, Inc. / Cardiovascular Research Institute Distinguished Research Center (DRC)
Sponsor:  Takeda Pharmaceuticals, Inc.
Principal Investigator:  Dr. Burton E. Sobel

Publications:

Representative Publications from a Total of 937

Shell WE, Kjekshus JK, Sobel BE:  Quantitative assessment of the extent of myocardial infarction in the conscious dog by means of analysis of serial changes in serum creatine phosphokinase activity.  J. Clin. Invest. 50:2614-2626, 1971.

Bergmann SR, Fox KAA, Ter-Pogossian MM, Sobel BE (Washington University), Collen D (University of Leuven):   Clot-selective coronary thrombolysis with tissue-type plasminogen activator.  Science 220:1181-1183, 1983.

Van de Werf F, Ludbrook PA, Bergmann SR, Tiefenbrunn AJ, Fox KAA, de Geest H, Verstraete M, Collen D, Sobel BE: Coronary thrombolysis with tissue-type plasminogen activator in patients with evolving myocardial infarction.  N. Engl. J. Med. 310:609-613, 1984.

Schneider DJ, Sobel BE:  Augmentation of synthesis of plasminogen activator inhibitor type-1 by insulin and insulin-like growth factor type-1 and its pathogenetic implications for diabetic vascular disease.  Proc. Natl. Acad. Sci. USA 88:9959-9963, 1991.

McGill JB, Schneider DJ, Arfken CL, Lucore CL, Sobel BE:  Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients.  Diabetes 43:104-109, 1994.

Sobel BE, Woodcock-Mitchell J, Schneider DJ, Holt RE, Marutsuka K, Gold H: Increased plasminogen activator inhibitor type-1 in coronary artery atherectomy specimens from type 2 diabetic compared with nondiabetic patients: A potential factor predisposing to thrombosis and its persistence. Circulation 97:2213-2221,1998.

Sobel BE for the BARI 2D Trial Investigators: Ancillary studies in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial: Synergies and opportunities.  Am. J. Cardiol. 97(Suppl.):53G-58G, 2006.

Dong J, Fujii S, Imagawa S, Matsumoto S, Matsushita M, Todo S, Tsutsui H, Sobel BE: Interleukin (IL)-1 and IL-6 induction of plasminogen activator inhibitor-1 in hepatocytes through a statin sensitive signaling pathway: Implications for clinical effects.  Am. J. Physiol. 292:C209-C215, 2007.

Zaman AKMT, Fujii S, Schneider DJ, Taatjes DJ, Lijnen HR, Sobel BE:  Deleterious effects of lack of cardiac PAI-1 after coronary occlusion in mice and their pathophysiologic determinants.  Histochem. Cell Biol. 128:135-145, 2007.

The BARI 2D Investigators:  Baseline characteristics of patients with diabetes and coronary artery disease enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.  Am. Heart J. 156:528-536, 2008.