The vascular endothelium, once thought to be a thin layer of quiescent cells present only to allow smooth, laminar blood flow has been discovered to be a central regulator of vascular homeostasis. Both traditional and novel cardiovascular risk factors have been shown to induce the endothelium to take on a phenotype characterized by inflammation, pro-thrombotic stimuli, and vasoconstriction.
This state of endothelial “dysfunction” has been shown to precede the development of atherosclerosis and portend cardiovascular events in both those with and without clinically evident cardiovascular disease. Endothelium-derived nitric oxide (EDNO) has been shown to be a central paracrine hormone in the maintenance of normal endothelial function, and a central characteristic of endothelial dysfunction is a reduction in bioavailable EDNO. Measuring EDNO bioavailability in larger conduit vessels and in the microvasculature in vivo can be accomplished by multiple modalities, including high-resolution vascular ultrasound and venous plethysmography.
We employ these methodologies to investigate the pathophysiological mechanisms underlying the development of endothelial dysfunction in humans with a variety of disease states, including coronary artery disease and diabetes.
The role of disturbances in mitochondrial homeostasis in the development of endothelial dysfunction in humans with type 2 diabetes.
The mechanisms of endothelial dysfunction related to the development of hyperglycemia and hypoglycemia.
The role of aldosterone in mediating the endothelial dysfunction of African Americans with hypertension.
Our human vascular research laboratory has been formed to foster collaboration with investigators from other disciplines interested in the impact of vascular function on disease states relevant to their fields of interest. Current collaborative efforts include work with investigators from disciplines including Orthopedics, Geriatrics, Endocrinology, Pediatric Endocrinology, and Pediatric Cardiology. We have also established collaborative relationships with investigators at UW-Milwaukee on projects related to the effect of exercise on vascular endothelial function in older adults.