Fellowship Ahmed Ismaeel: BRASSICA: Broccoli to Attenuate Arterial Stiffness in Limb Ischemia

This research proposal tests the overall hypothesis that reduced nrf2 expression and activation is involved in arterial dysfunction in PAD, by increasing vascular collagen production. We will test whether broccoli sprout consumption, which contains the nrf2 activator sulforaphane, can improve arterial stiffness in a murine hindlimb ischemia model. We will follow this work with mechanistic studies in an in vitro model of ischemia-reperfusion and assess the mechanism of sulforaphane action by inducing knockdown of specific genes and by trapping and visualizing the products released from sulforaphane. A professional development program and individual mentoring round out the career development plan for successful transition to an independent academician. Priority area focus: Food safety, nutrition, and health Program area/AFRI EWD relevance: This project is aligned to the AFRI EWD overarching goal of advancing science. This work will give insights into the mechanisms of sulforaphane’s action. Peripheral artery disease is a growing health problem, and this project will identify whether sulforaphane may be a viable therapeutic approach in the context of limb ischemia, by targeting the pathophysiological mechanism of arterial dysfunction. This work will also inform future studies to test whether sulforaphane-containing cruciferous vegetables, such as broccoli/broccoli sprouts, may improve walking performance in peripheral artery disease patients. Additionally, the formal career development program outlined will allow the candidate to systematically develop skills necessary for PI development as an independent tenure-track investigator and teacher.