sFLT-1-based experimental models of preeclampsia: biological relevance, limitations, and implications for model selection

Abstract

Preeclampsia is a pregnancy-associated disorder characterized by hypertension and multisystem maternal complications. Soluble fms-like tyrosine kinase-1 (sFLT-1) is widely used to establish experimental animal models, since elevated circulating sFLT-1 reproducibly induces endothelial dysfunction, hypertension, proteinuria, and glomerular injury. These findings indicate that angiogenic imbalance can generate the maternal syndrome of the disease. However, preeclampsia originates from abnormal placentation, whereas sFLT-1 primarily mediates the maternal systemic response. To clarify the biological meaning of these models, published sFLT-1 animal models were evaluated from four aspects: species differences, source of expression, placenta specificity, and isoform variation. The analysis showed that systemic sFLT-1 overexpression models reliably reproduce maternal vascular and renal manifestations but lack primary placental pathology. In contrast, placenta-restricted expression improves physiological relevance but still bypasses upstream mechanisms of trophoblast invasion failure. Therefore, sFLT-1 models do not represent the entire disease process and instead correspond to a specific pathological stage. These models are suitable for studying endothelial injury, renal pathology, and angiogenic-targeted interventions but are limited in investigating disease initiation, immune maladaptation, and clinical heterogeneity. Recognizing these boundaries can improve model selection and interpretation in experimental preeclampsia research.

Keywords

preeclampsia / animal model / sFLT-1 / angiogenic imbalance / endothelial dysfunction / placentation

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