MON-292 - Exploring the Role of Glucocorticoid-HMGB1 Signaling in Endothelial Angiogenic Dysfunction: A Model for Vascular Stress in Preeclampsia

Preeclampsia is a hypertensive disorder of pregnancy marked by systemic endothelial dysfunction and an increased risk of long-term maternal cardiovascular disease. Chronic maternal stress and dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity in preeclampsia result in sustained glucocorticoid (GC) exposure, yet the mechanisms linking GC signaling to endothelial dysfunction remain incompletely understood. Emerging evidence suggests that prolonged GC exposure may alter glucocorticoid receptor (GR) dynamics, impairing anti-inflammatory pathways. One such mediator is high mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) implicated in vascular inflammation and angiogenic imbalance in preeclampsia. We hypothesize that chronic glucocorticoid exposure induces HMGB1 signaling through dysregulated glucocorticoid receptor (GR) pathways, resulting in impaired angiogenic capacity in endothelial cells.
This study aims to explore how chronic GC exposure affects GR signaling, HMGB1 expression and release, and angigenic function in human endothelial cells. Primary human umbilical vein endothelial cells (HUVECs) will be treated with dexamethasone to model chronic glucocorticoid exposure. GR signaling activity will be evaluated via NR3C1 and FKBP5 expression using an NCounter Pathway Panel. HMGB1 levels will be assessed in cell lysates and conditioned media, and angiogenic function will be measured through tube formation assays and VEGF expression anaylsis.
These studies study will provide preliminary mechanistic insight into GC-induced endothelial dysfunction and the role of HMGB1 in modulating angiogenic capacity. Findings may inform future in vivo investigations and therapeutic strategies targeting stress-responsive inflammatory signaling in preeclampsia.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*