FBXO38 Regulates Nox1 Stability to Reduce Vascular Endothelial Damage Induced by Low Oscillatory Shear Stress.

Oxidative stress and endothelial dysfunction are critical drivers of atherosclerosis, but the mechanisms regulating oxidative stress under disturbed flow conditions remain incompletely understood. The ubiquitin-proteasome system, particularly E3 ubiquitin ligases, may play a pivotal role in modulating these processes. FBXO38, an E3 ligase involved in proteasomal degradation, has been implicated in various physiological pathways, but its role in regulating oxidative stress in endothelial cells is unknown. We hypothesized that FBXO38 mitigates endothelial damage induced by low oscillatory shear stress (LOSS) by promoting the ubiquitin-proteasome-dependent degradation of Nox1, a major source of reactive oxygen species (ROS). Using an in vitro LOSS model in human umbilical vein endothelial cells (HUVECs) and an in vivo mouse partial carotid ligation model, we assessed the expression of FBXO38 and Nox1 through quantitative PCR, western blotting, immunofluorescence, and immunohistochemistry. LOSS significantly reduced FBXO38 protein expression (by ~60%,