David G. Harrison, MD, FACC, FAHA, is the Director of the Division of Clinical Pharmacology within the Department of Medicine at Vanderbilt University Medical Center.
His research laboratory has been focused on understanding how inflammation, and in particular, the adaptive immune response contributes to hypertension. Several years ago, they found that T cells are essential for the development of hypertension. His lab has shown that various hypertensive stimuli, including angiotensin II, norepinephrine and DOCA-salt cause activation of T cells and leads to their accumulation in the perivascular fat and kidneys. The data indicates that T cell-derived cytokines such as IL-17 and TNF-a enhance vasoconstriction and sodium retention, leading to the hypertensive phenotype. Central signals derived from the circumventricular organs contribute to T cell activation, and manipulation of signals from this region affect T cell activation and the eventual elevation in blood pressure caused by angiotensin II.
Dr. Harrison’s lab is studying mechanisms involved in T cell activation in response to hypertensive stimuli. They have recently shown that gamma-ketoaldehydes, or isoketals adduct to proteins in hypertensive mice and humans, and that these are immunogenic. These modified proteins seem to act as 'auto-antigens' that promote dendritic cell and ultimately T cell activation in hypertension.