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

Mi Zhang; Caijing Wu; Jialing Liu; Yu Wang; Peiying Ye; Qixuan Yue; Huijie Xu; Xingzheng Gu; Yihua Zhu; Jie Tang; Guanglei Li; Weihua Zhao; Mi Zhang; Caijing Wu; Jialing Liu; Yu Wang; Peiying Ye; Qixuan Yue; Huijie Xu; Xingzheng Gu; Yihua Zhu; Jie Tang; Guanglei Li; Weihua Zhao

doi:10.3934/bioeng.2026010

AIMS Bioengineering

2026, Volume 13, Issue 2: 239-256. doi: 10.3934/bioeng.2026010

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

1.
Guangxi University of Chinese Medicine, Nanning 530200, China
2.
Shenzhen University, Shenzhen 518055, China
3.
Department of Obstetrics, Shenzhen Second People's Hospital / The First Affiliated Hospital of Shenzhen University, Key Unit of Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Shenzhen 518035, China
4.
Shenzhen Technology University, Shenzhen 518118, China

Received: 28 February 2026 Revised: 19 May 2026 Accepted: 03 June 2026 Published: 18 June 2026

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.
- preeclampsia,
- animal model,
- sFLT-1,
- angiogenic imbalance,
- endothelial dysfunction,
- placentation
Citation: Mi Zhang, Caijing Wu, Jialing Liu, Yu Wang, Peiying Ye, Qixuan Yue, Huijie Xu, Xingzheng Gu, Yihua Zhu, Jie Tang, Guanglei Li, Weihua Zhao. sFLT-1-based experimental models of preeclampsia: biological relevance, limitations, and implications for model selection[J]. AIMS Bioengineering, 2026, 13(2): 239-256. doi: 10.3934/bioeng.2026010

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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.

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Conflict of interest

The authors declare no conflict of interest.

Author contributions

Mi Zhang and Weihua Zhao conceived the study. Mi Zhang performed the literature search, data collection, and drafted the manuscript. Caijing Wu and Jialing Liu contributed to literature screening and data organization. Yu Wang, Peiying Ye, Qixuan Yue, Huijie Xu and Xingzheng Gu participated in data interpretation and manuscript revision. Yihua Zhu and Jie Tang contributed to critical revision of the manuscript and provided academic guidance. Guanglei Li supervised the study and revised the manuscript for important intellectual content. Weihua Zhao was responsible for overall project design, coordination, and final approval of the manuscript. All authors read and approved the final version of the manuscript.

Funding

This work was supported by the Science and Technology Planning Project of Guangdong Province, China (Grant Number: 2023B110010) and the Medical and Health Science and Technology Development Research Center, National Health and Family Planning Commission of China (Grant No. W2016CWGD09).

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