Vascular Biology Program

Investigators in the Emory Pulmonary, Allergy. Critical Care and Sleep Medicine Division are exploring basic mechanisms of vascular dysfunction in the systemic and pulmonary circulations. In the systemic vasculature, atherosclerosis and its clinical manifestations including coronary artery diease and myocardial infarction, cerebrovascular disease and stroke, and peripheral vascular disease are major causes of morbidity and mortality in the United States. Although less prevalent than disorders associated with systemic vascular disease, pulmonary hypertension is an often progressive and fatal disorder for which new therapies are urgently needed.

The focus of vascular biology investigation in the Emory Pulmonary, Allergy, Critical Care and Sleep Medicine Division centers on endothelial dysfunction which constitutes an early derangement common to disorders of systemic and pulmonary vascular disease. Under normal conditions, the vascular endothelium synthesizes a balanced mix of vasoconstricting and vasodilating substances. This balanced production of vasoactive mediators is disturbed early in the course of vascular disease resulting in enhanced production of vasoconstricting mediators and reduced production of vasodilating mediators. These derangements not only disturb vascular reactivity but also modulate inflammation, signaling, and gene expression in the essel wall.  Current studies are focused on examining the role and sources of reactive oxygen and nitrogen species in the systemic and pulmonary circulations and how alterations in these mediators contribute to alter vascular function and disease pathogenesis.

Active projects are focused on the following broad themes:

-The role of PPARy in vascular superoxide production in diabetes
-The role of PPARy in regulating endothelial function in pulmonary hypertension
-Mechanisms of pulmonary vascular disease and accelerated atherosclerosis in HIV infection
-The role of pendrin in salt-induced hypertension
-The mecahnisms for the development of diastolic dysfunction in an accelerated aging model
-The role of NADPH oxidase in pulmonary hypertension caused by chronic intermittent hypoxia
-The contribution of altered reactive species production to systemic and pulmonary vascular derangements caused by chronic alcohol ingestion

Models include wilde type and knockout or transgenic rodent models exposed to chronic hypoxia as a stimulus for the development of pulmonary hypertension. In vitro studies employ cultured cells from the vascular wall including endothelial and vascular smooth muscle cells. Techniques employed involved physiological, cell and molecular biology approaches to explore mechanistic hypotheses. Approaches include measurements of systemic and pulmonary vascular pressures, vascular ring reactivity, lung resistance and compliance determinations, measurement of reactive oxygen and nitrogen species in cells and tissues using electron spin resonance spectroscopy, analysis of signaling pathways, gene and protein expression, to name a few.