Endothelial Dysfunction: Insights into Systemic Lupus Erythematosus-associated Cardiovascular Disease and Neuropsychiatric Manifestations

Cardiovascular disease (CVD) and neuropsychiatric manifestations are common in patients with Systemic Lupus Erythematosus (SLE), often sharing a vascular origin with endothelial dysfunction central to their development. The endothelium plays a critical role in regulating systemic and cerebral blood flow and influencing end-organ damage in SLE. In this review, we summarize foundational and recent studies linking vascular dysfunction to CVD and neuropsychiatric outcomes, emphasizing the roles of endothelial activation, endothelial progenitor cells, blood-brain barrier dysfunction, and vascular autoantibodies. We also highlight animal models that facilitate the study of vascular and cerebral manifestations, clarifying the interconnected contributions of endothelial health to SLE-related organ damage. Finally, we discuss emerging therapeutic strategies aimed at restoring endothelial function to improve cardiovascular and neuropsychiatric outcomes in SLE.