Role of Inflammation in Hypertension
Hypertension is one the leading causes of mortality in the US. One in three people suffer from high blood pressure, which is correlated to the development of other diseases such as diabetes, renal damage, and obesity. My laboratory has shown that T cells play an important role in hypertension, but the mechanisms by which they are activated remains undefined. Dendritic cells present antigens and secrete cytokines that modify T cell polarization. The NADPH oxidase contributes to hypertension via multiple mechanisms. Hypertensive mice have high levels of superoxides. Superoxide catalyzes the formation of H2-isoprostanes, which rearrange to form reactive γ-ketoaldehydes termed isoketals that adduct to protein lysines which renders them immunogenic. We hypothesize that oxidative stress catalyzes the formation of isoketals, which alters the function of dendritic cells leading to inflammation and hypertension. Therefore, my project focuses on identifying the molecular and physiological mechanism by which isoketals function during hypertension.