Education / Training

• 1994, B.A. in Biology, University of North Texas, Denton, Texas
• 1997, Ph.D. in Physiology, University of North Texas Health Science Center, Fort Worth, Texas
• 1997-2000, Postdoctoral Fellowship in Physiology, University of Washington School of Medicine, Seattle, WA

Research Description

The long-term goal our research is to delineate mechanisms of obesity-related coronary vascular disease and thereby elucidate pathways and novel therapeutic targets to reduce the incidence of cardiovascular complications in this patient population. The central premise of our studies is that impaired coronary microvascular function is an important contributor to increased cardiovascular morbidity and mortality in obese patients with the metabolic syndrome. Since the myocardium has a very limited anaerobic capacity, the heart is highly dependent on a continuous supply of oxygen from the coronary circulation to meet its metabolic requirements. If this need for oxygen is not met, the resulting underperfusion/ischemia substantially diminishes cardiac function within seconds. Thus, tight control of coronary blood flow is essential to maintain myocardial performance. Indeed, earlier studies from our laboratory documented that induction of the metabolic syndrome markedly impairs the ability of the coronary circulation to adequately balance myocardial oxygen delivery with myocardial metabolism at rest and during exercise-induced increases in cardiac metabolic demand. More recent studies demonstrate that this impairment in the control of coronary blood flow that is related to activation of the renin-angiotensin and sympathetic nervous system as well as augmented levels of adipocytokines. Our ongoing studies are focused on how specific K⁺ channels and perivascular adipose tissue contribute to the development of coronary disease in the metabolic syndrome. These studies utilize integrative in vivo and in vitro approaches as well as molecular biology techniques to investigate the role of these systems in obesity-induced coronary vascular dysfunction and disease.

Response of coronary blood flow and aortic pressure to graded treadmill exercise. Data from Tune et al. Am. J. Physiol. Heart Circ. Physiol. 278: H74-H84, 2000.

         

Recent data demonstrating the progressive decline of the coronary reactive hyperemic response in B) short-term vs. C) long-term metabolic syndrome (MetS) Ossabaw swine.
       

Picture of isolated coronary arteries without (A) and with (B) normal surrounding perivascular adipose tissue. Adipose tissue significantly impairs coronary endothelial-dependent vasodilation to bradykinin in arteries from Ossabaw swine with metabolic syndrome (C).

Whole cell patch-clamp recordings show diminished outward K⁺ current in isolated coronary vascular smooth muscle cells from Ossabaw swine with the metabolic syndrome (data collected in collaboration with Sturek Lab). Representative confocal images demonstrating depressed membrane trafficking of
BK_Ca channel α and β1 subunits.

       

Recent Publications >