Table 1.
Summary of animal models of preeclampsia
| Model | HTN | Proteinuria | Endothelial dysfunction | IUGR | Angiogenic imbalance | Additional phenotypes | Therapeutics tested | References | |
|---|---|---|---|---|---|---|---|---|---|
| Immune mediated | Low-dose LPS | ✓ | ✓ | ? | ✓ | ✓ | ↑ renal injury, ↑ fetal resorptions | Low-dose aspirin, quercitin, lipoxin A4, curcumin, metformin, nicotine, galectin 9 | (11-22) |
| TLR 3, 7, and 8 stimulation | ✓ | ✓ | ✓ | ✗ | ? | ↑ fetal demise, placental inflammation, systemic inflammation | IL-4 and IL-10 cosupplementation, MHC class II invariant chain depletion, γ δ T-cell depletion | (23-26) | |
| TLR9 stimulation | ✓ | ✓ | ✗ | ✗ | ✓ | Excess vasoconstriction and oxidative stress, placental inflammation, ↑ fetal resorptions | Low-dose aspirin | (27, 28) | |
| C1q –/– mouse | ✓ | ✓ | ✓ | ✓ | ✓ | ↑endotheliosis, ↑fetal death | Pravastatin, L-citrulline | (29–31) | |
| TNF-α infusion | ✓ | ✓ | ✓ | ✗ | Mild | ↓ GFR, ↓ renal plasma flow, ↑ HIF-1α | Endothelin A receptor antagonist, HO-1 induction | (32–37) | |
| IL-10 –/– mouse | ✓ | ✓ | ✓ | ✗ | ? | Placental inflammation, systemic inflammation | (38) | ||
| IL-4 –/– mouse | ✓ | ✓ | ✓ | ✗ | ? | Placental inflammation, systemic inflammation | (39) | ||
| Spontaneous/genetic | BPH/5 mouse | ✓ | ✓ | ✓ | ✓ | ✓ | Abnormal spiral artery remodeling, complement activation at maternal/fetal interface, hyperleptinemia | Tempol, Cox2 inhibition, complement inhibition | (40-43) |
| Dahl S rat | ✓ | ✓ | ✓ | ✓ | ✓ | ↑ uterine artery resistance, glomerulomegaly, placental hypoxia | PDE5 inhibition, sodium thiosulfate, L-citrulline, 1,3-butanediol | (44-49) | |
| Surgical/pharmacological | L-NAME infusion | ✓ | ✓ | ✓ | ✓ | ✓ | ↓ placental weight | L-arginine, PDE5 inhibition, vagus nerve stimulation, VEGF, fibroblast growth factor type 2 | (50–59) |
| Arginine vasopressin | ✓ | Mild | ✗ | ✓ | ✗ | Impaired spiral artery remodeling | None | (60, 61) | |
| sFlt-1 overexpression/infusion | ✓ | ✓ | ✓ | ✓ | ✓ | ↓ placental weight, ↑ ET-1, ↑ ROS | Pravastatin, HO-induction, VEGF | (62-66) | |
| Uterine artery ligation | ✓ | ✓ | ? | ? | ✓ | PlGF, sFlt-1 siRNA | (67-69) | ||
| Reduced uterine perfusion pressure | ✓ | ✓ | ✓ | ✓ | ✓ | ↑ peripheral vascular resistance, ↑ ET-1, ↓NO, ↓ GFR, ↓ RPF, ↑ inflammatory cytokines, ↑ BBB permeability | Endothelin type A receptor blockade, L-arginine, TNF-ɑ blockade, tempol, HO-1 induction, L-ergothioneine, VEGF, pravastatin, PlGF, nicotine, neutrophil depletion, complement inhibition | (66, 70-81) |
Abbreviations: ✓, present; ✗, absent; ?, unknown or not tested; BBB, blood-brain barrier; Dahl S, Dahl salt-sensitive; ET-1, endothelin-1; GFR, glomerular filtration rate; HTN, hypertension; IL, interleukin; IUGR, intrauterine growth restriction; L-NAME, N-nitro-L-arginine methyl ester; LPS, lipopolysaccharide; NO, nitric oxide; PDE5, phosphodiesterase 5; PlGF, placental growth factor; ROS, reactive oxygen species; RPF, renal plasma flow; siRNA, small interfering RNA; sFlt-1, soluble fms-like tyrosine kinase-1; TLR, toll-like receptor; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.