Table 2.
The potential targets and drugs for APS therapy.
| Inhibitors | Targets | Mechanisms | Effects | Refs |
|---|---|---|---|---|
| Hyperoside | mTOR/S6K, TLR4/MyD88/NF-kB | downregulate the expressions of phosphorylated mTOR, phosphorylated p70S6 Kinase and reduce the levels of MyD88, TLR4, and phosphorylated NF-kB p65. | improved pregnancy outcome, including a lower rate of fetal resorption and increased fetal weight. | (134) |
| stimulate the occurrence of cellular autophagy while concurrently hindering the nuclear translocation and phosphorylation and of NF-κB p65 | reduced expression of inflammatory factors and endothelial adhesion molecules, such as IL-6, TF, VCAM-1, etc. | (121) | ||
| Vitamin D | TLR4/MyD88 | inhibit the TLR4/MyD88 signaling pathway, thereby reducing TF release downstream and diminishing ECs activation effects. | limit inflammation and subsequent adverse outcomes in APS pregnancies | (135, 136) |
| Peptides that target domain V of beta-2-glycoprotein I | domain V of beta-2-glycoprotein I | block Domain V from binding to cell surfaces | decreased β2GPI binding to ECs, diminished interaction between aPL and human trophoblast, and attenuated capacity of aPL to induce thrombosis or fetal loss in murine models | (137, 138) |
| Peptides that target domain I of beta-2-glycoprotein I | domain I of beta-2-glycoprotein I | block binding of APS-IgG to β2GPI | suppress the thrombotic-promoting capacity of APS-IgG | (139) |
| monoclonal antibody | beta-2-glycoprotein I | prevent the formation of pathogenic complexes involving relevant antibodies and β2GPI | diminished inhibitory effect of aPL on EC migration, and reversed impairment in reendothelialization caused by aPL | (140) |
| beta-2-glycoprotein I | prevents binding to the complement, but has a high affinity with β2GPI | loss of procoagulant and proabortive effects | (141) | |
| IFN-α | Target IFN, blocking downstream cascading reactions | reduced expression level of IFN and symptom relief | (142–148) | |
| Sirolimus、RapaLink-1(mTOR Inhibitors) | mTOR | promotes autophagy via inhibit mTOR | reduced size of thrombus and lower antibody concentration | (149–154) |
| miRNAs | TLR-7 and TLR-9 | miRNA is an important epigenetic regulatory factor in the mRNA transcription, capable of modulating downstream TLR-mediated IFN generation | reduced IFN-scores, a significant factor influencing both subclinical and clinical manifestations in APS | (155) |
| TF-inhibitor NAPc2 | tissue factor | specific blockade of the TF coagulation initiation complex | diminished prothrombotic effects of aPL and the aPL–induced proinflammatory activation | (156) |
| αEPCR 1496 | EPCR | inhibit the effect of EPCR by binding with it | reduced expression of TNF, F3, IFR8, and GPB6 | (93) |
| plasminogen activator-coated nanobubbles | beta-2-glycoprotein I | rtPA-coated nanobubbles targeting cell-bound β2GPI clear occluded vessels | reduction of new thrombosis, recanalization of occluded blood vessels, and reduction of fibrin deposition | (157) |
| antagonist for LRP8 ligand binding | LRP8 | inhibit the action of LRP8 as a receptor | inhibited phosphorylation of LRP8 and Dab, prevent the overexpression of TF, IL-6 and adhesion molecules | (56, 158) |
| statins, methyl-β-cyclodextrin | lipid raft | damage the structure of the lipid raft through inhibiting cholesterol synthesis or depleting membrane cholesterol | inhibited phosphorylation of LRP8 and Dab, prevent the overexpression of TF, IL-6 and adhesion molecules | (56, 158) |
| pravastatin, low molecular weight heparin and low dose aspirin | eNOS/NO | increase eNOS synthesis and activity, resulting in a substantial rise in nitric oxide (NO) production. | improved placental haemodynamics, ameliorated preeclampsia symptoms and improved fetal growth | (159) |