497 From hypertension to fibroids: Translating cardiovascular therapeutics for women’s health

Objectives/Goals: To investigate renin–angiotensin system (RAS) modulation as a therapeutic target for uterine fibroids using a xenograft model, translating insights from cardiometabolic–fibroid comorbidity into accessible treatment strategies for underserved populations. Methods/Study Population: We established a xenograft model by implanting matched human fibroid and myometrial tissue into NOG mice (n=6 per group) supplemented with estrogen pellets. This translational model mimics the clinical context of hypertensive patients with fibroids treated with RAS-modulating drugs. Mice were randomized to receive angiotensin II, losartan, enalapril, or vehicle control. Tumor volumes were measured weekly by caliper. At endpoint, xenografts are analyzed for proliferation (Ki67), fibrosis (α-SMA, collagen), and immune composition using flow cytometry and immunofluorescence. Results/Anticipated Results: Preliminary data from all 24 mice reveal variable fibroid xenograft growth across treatment groups, with no consistent dose–response pattern in gross tumor volumes. Ongoing molecular and cellular analyses may uncover treatment effects not reflected in volume measurements alone. Final analyses will integrate proliferative indices, fibrotic markers, and immune cell profiles to determine whether RAS modulation influences fibroid biology at the cellular level despite heterogeneous morphological responses. Discussion/Significance of Impact: Fibroids disproportionately affect Black women and are closely linked to cardiovascular disease. Repurposing FDA-approved antihypertensives offers an accessible, low-cost therapeutic avenue and exemplifies translational science by bridging mechanistic discovery with equitable treatment innovation.