Determining the effects of pre-diabetic metabolic disease on vascular function: While insulin resistance is well-recognized as a precursor state to diabetes, emerging evidence indicates that it is also a risk factor for cardiovascular disease. Using dietary models of sugar loading, evidence has mounting of impaired control of endothelial function and altered regulation of blood pressure in insulin resistance. What remains unclear is the extent to which the vascular dysfunction in obesity can be attributed to the metabolic changes associated with obesity. To address this issue, we have generated dual transgene mice on a eptin-deficient background. The second transgene is Protein Tyrosine Phosphotase 1-B, a key regulatory enzyme that causes insulin resistance. By deleting this enzyme, a strain of mice is generated that is still obese (Mouse #250) compared to control (Mouse #24) but insulin sensitive with a normal metabolic profile. The next phase of these studied will determine if cardiovascular dysfunction observed in normal obese mice (#248) are corrected in the dual transgene.

Endocrine dysfunction as a cause of cardiovascular disease in obesity: While metabolic function is well-known to accompany increases in adiposity, it is also known that other, parallel endocrinopathy occurs. Our lab is interested in two specific kinds of endocrine disease: hypothyroidism and hyperadrenalism. Both conditions are evident on obese individuals but the cardiovascular consequences are unknown. The specific interest in our lab is the extent to which these two condition impact on signaling in the adrenergic receptor pathways present in vascular smooth muscle. Alpha adrenergic tone is upregulated in the skeletal muscle circulation and alpha adrenergic receptors are at least in part regulating by glucorticoids, the hormones that are increased in hyperadrenal states. In contrast, beta adrenergic vasodilation is reduced in obesity and beta adrenergic receptor expression is determined by thyroid status, which is reduced in obesity. Thus, the shift to a more constricted state may be driven by an imbalance in these two hormone system. The goal of this project is to determine the extent to which normalization of hormone status improves cardiovascular function in obesity.

Regulation of cardiovascular during stress: Another cardiovascular deficit in obese individuals is the inability to properly regulate blood pressure during periods of psychological stress. Obesity appears to impair the proper integration of neural and vascular signal during periods of psychological stress and thus normal events can precipitate cardiovascular exigencies in obese individuals. In this project, we are attempting to determine the extent to which neural control of the circulation is altered at the vascular level and whether this dysfunction contributes to impairment in both the acute and chronic regulation of blood pressure.


Adrenal Gland from an Obese rat

• Virendra Mahesh Distinguished Research Award, MCG - 2010
•  Featured research: National report of the AHA Wisconsin Affiliate – 2001
• Microcirculation Society Young Investigator Travel Award – $2500 to defray the costs of a lecture tour across Europe – September 2001
• Lamport Award for Outstanding Young Physiologist finalist - 1997
• American Heart Association Fellowship 1996-1997 (Declined)
• American Heart Association Fellowship 1995-1996
• NIH training grant appointee, Center for Bioengineering, University of Washington, 1993-1995 – J.B. Bassingthewaite, P.I.
• Teaching assistantship, Medical College of Pennsylvania, 1988-1993

“Compensatory Interactions in the Coronary Microcirculation”

• Medtronics, Inc., Minneapolis, MN – February 2000
• Bristol Meyers-Squibb, Princeton, NJ – March 2000
• Wyeth Pharmaceutical, Lawrenceville, PA – July 2000
• West Virginia University, Morgantown WV – August 2000
• Abbot Laboratories, Chicago IL – October 2000
• University of South Carolina, SC – November 2000
• Eastern Virginia Medical School, Norfolk VA – February 2001
• Indiana University, Indianapolis, IN – March 2001
• Medical College of Georgia, Augusta GA – May 2001
• Erasmus University, Rotterdam, The Netherlands – September 2001
• Academic Medical Center, Amsterdam, The Netherlands – September 2001
• Institut für Kardiovaskuläre Physiologie, Frankfurt, Germany – September 2001
• Institut de Recherce Servier, Paris, France – September 2001
• International Society of Heart Research, Szeged, Hungary - July 2002

“Is Shear Stress A Regulated Variable in the Coronary Microcirculation?”

• International Society of Heart Research, Louisville, KY – June 2000
• National Institutes of Health – August 2002

“Microvascular Structural and Functional Alterations in Syndrome X”

• Lankenau Research Institue, Philadelphia, PA - October 2001
• Medical College of Georgia, Augusta GA - November 2001
• University of South Carolina –Aiken –March 2002
• University of Cincinnati – Cincinnati – January 2003
• University of Mississippi Medical Center – Jackson, MS – August 2003
• Louisiana Health Sciences Center – New Orleans, LA – August 2003
• American Heart Association National Meeting – New Orleans, LA – November 2004 (abbreviated form)
• University of Georgia – Athens, GA – February 2006

“Oxidant Stress in the Metabolic Syndrome X”

• Southeastern Lipid Research Club, Georgia – September 2003

“Impact of Obesity on Control of Blood Flow”

• Texas A&M University, Temple, TX – September 2005
• Virginia Commonwealth University, Richmond, VA – September 2005
• American Heart Association National Meeting – Dallas, TX – November 2005 (abbreviated form)
• Experimental Biology – San Francisco, CA, April 2006 (abbreviated form)
• European Council on the Microcirculation – Amsterdam, The Netherlands, August 2006
• Case Western Reserve University – Cleveland, OH – November 2006

“The Effects of the Metabolic Syndrome on the Microcirculation”

• 8th World Congress on the Microcirculation – Milwaukee, WI – August 2007
• American Heart Association National Meeting – Orlando, FL – November 2007
• European Council on the Microcirculation, Budapest, Hungary - August 2008
• Morehouse University, Atlanta GA – October 2008
• University of Alabama, Birmingham, AL – March 2009
• University of Sao Paulo, Riberio Preto,Brazil – October 2010
• University of North Texas HSC, Fort Worth TX – February 2011
• University of South Carolina, Columbia, SC – April 2011
• Experimental Biology 2011– Washington DC April 2011

“Novel Links between Obesity and Cardiovascular Function”

• 42nd Annual Brazilian Congress on Experimental Pharmacology and Therapeutics, Ribeirão Preto, Brazil – October 2010 Global
• Obesity Summit, Jackson MS – November 2010

James Mintz

Nitirut Nernpermpisooth

Christina Salet

Shuiqing Qiu