Angiogenic imbalance and endothelial dysfunction in the placenta in antiphospholipid syndrome.

Placental vascular development depends on the tightly orchestrated interplay of vasculogenesis, angiogenesis, and vascular remodeling to sustain efficient maternal-fetal exchange across gestation. In obstetric antiphospholipid syndrome (APS), antiphospholipid antibodies (aPL) function as active pathogenic mediators that perturb this program by promoting endothelial activation, immune-driven injury, and a shift toward angiogenic imbalance. This review summarizes the fundamental mechanisms governing normal placental vascular development, emphasizing the coordinated roles of uterine immune cells and extravillous trophoblasts. Accumulating evidence indicates that aPL-β2GPI interactions promote NF-κB-dependent inflammatory and prothrombotic endothelial responses, accompanied by complement and inflammasome activation, oxidative stress, and NET-associated vascular injury. At the clinical level, pregnancies complicated by APS frequently display a preeclampsia-like anti-angiogenic profile, characterized by elevated sFlt-1, reduced PlGF, and increased sFlt-1/PlGF ratios, which often precede clinical manifestations and associate with placental insufficiency, fetal growth restriction, and pregnancy loss.