John F. Keaney, Jr., MD

Medical Director, Heart and Vascular Center of Excellence Division Chief, Cardiovascular Medicine
University of Massachusetts Medical School and University of Massachusetts Memorial Medical Center
Mary C. DeFeudis Professor of Biomedical Research University of Massachusetts Medical School, Worcester, MA

 image of Dr. John Keaney
Abstract: Cardiovascular disease remains the number one source of morbidity and mortality in the developed world. A key control point for the development of atherosclerosis and its clinical sequelae is vascular function that resists thrombosis, inflammation, and vasospasm. In collaboration with Balz Frei and Joseph Vita, we embarked on a research program to investigate how the redox environment of the endothelium dictates vascular function. We found that normal vascular homeostasis was dependent upon both the extracellular presence of reactive oxygen species and the intracellular redox state, dictated largely by small molecule antioxidants. Using combinations of studies in cell culture and human subjects, the roles of ascorbic acid, glutathione, and tetrahydrobiopterin was elucidated. More recently, this program has probed the involvement of mitochondria and stress-activated signaling pathways in the control of vascular function.