Targeting Complement Component 1q Ameliorates Diabetic Endothelial Inflammation Via Orphan Nuclear Receptor 4a1–Dependent Suppression of Nuclear Factor κB Signaling

BACKGROUND: Vascular inflammation triggers endothelial dysfunction, a pivotal factor in the pathogenesis of diabetic vascular complications. Complement component 1q (C1q), a crucial component of the immune system, is implicated in inflammation and immune responses. However, its role in modulating endothelial function in diabetes remains poorly understood. In this study, we aimed to investigate how C1q influences endothelial inflammation in diabetes and the underlying signaling mechanisms involved. METHODS: Gene expression in the aortas of streptozotocin-induced mice or primary endothelial cells was detected using real-time quantitative polymerase chain reaction, western blot, and immunofluorescence staining. Molecular docking identified dl-citrulline as a target for C1qa. Dihydroethidium staining was used to assess vascular reactive oxygen species generation, while Evans blue staining was used to evaluate vascular permeability. RESULTS: (homeobox a3), an upstream negative regulator of C1q transcription, protects against diabetic vascular injury. CONCLUSIONS: Together, these findings highlight that C1q downregulation ameliorates endothelial inflammation in diabetes, providing mechanistic insights for developing therapeutic strategies against diabetic vascular complications.