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Review Open Access

Role of monocytes in the pathogenesis of antiphospholipid syndrome and potential therapeutic targets (Review)

  • Authors:
    • Rongxiu Huo
    • Chengcheng Wei
    • Yanting Yang
    • Yang Yang
    • Xiaocong Huo
    • Bangqin Wang
    • Danli Meng
    • Yijia Huang
    • Rongjun Huang
    • Jinying Lin
    • Xinxiang Huang
  • View Affiliations / Copyright

    Affiliations: Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
    Copyright: © Huo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 305
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    Published online on: September 2, 2025
       https://doi.org/10.3892/mmr.2025.13670
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Abstract

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized primarily by arterial and/or venous thrombosis, obstetric complications and persistent positivity for antiphospholipid antibodies (aPLs). It has been proposed that the pathogenesis of APS is closely associated with vascular endothelial cell activation, complement activation and platelet activation. Notably, APS may be key to understanding the relationship between innate immune cells, and thrombosis and obstetric complications. Monocytes are activated by aPLs, adopting a pro‑inflammatory and pro‑coagulant phenotype, and producing inflammatory cytokines; however, the exact mechanisms of action of monocytes in APS remain unclear. Monocytes may act as an intermediary, triggering immune dysregulation, closely linking them to thrombosis and obstetric complications. Therefore, a better understanding of the potential pathogenic role of monocytes in APS is required, which could assist clinicians in gaining deeper insights into the pathogenesis of APS and identifying new therapeutic targets. This may provide new options for the management of APS. Therefore, the present study aimed to review monocytes and their role in APS.
View Figures

Figure 1

Monocytes as potential therapeutic
targets for APS. Various drugs target distinct components of
monocytes, such as TNF-α, ROS, NLRP3 and mTOR, thereby suppressing
monocyte activation in APS, reducing the production of inflammatory
cytokines and concurrently decreasing the secretion of procoagulant
factors. This approach is anticipated to effectively inhibit
thrombosis and address obstetric complications. APS,
antiphospholipid syndrome; mTOR, mammalian target of rapamycin;
NLRP3, NOD-like receptor family pyrin domain containing 3; ROS,
reactive oxygen species.

Figure 2

Potential pathogenesis of thrombosis
in monocytes in APS. In APS, aPLs binds to the TLR of monocytes
through the β2GPI protein and activates NLRP3 and mTOR,
which can activate monocytes, and secrete pro-inflammatory and
pro-coagulant factors. Pro-inflammatory factors can damage
endothelial cells, thereby secreting EVs and transferring microRNAs
to monocytes, causing monocytes to release cytokines, chemokines
and TF, and eventually form a thrombus. β2GPI,
β-2-glycoprotein-I; aPL, antiphospholipid antibody; APS,
antiphospholipid syndrome; EV, extracellular vesicles; IFN,
interferon; mTOR, mammalian target of rapamycin; NLRP3, NOD-like
receptor family pyrin domain containing 3; Th, T helper; TLR,
Toll-like receptor; vWF, von Willebrand factor.

Figure 3

Potential pathogenesis of obstetric
complications in APS mediated by monocytes. In APS, aPLs activate
the complement pathway, leading to the formation of inflammatory
fragments such as C3a and C5a. These fragments not only deposit in
the placenta but also bind to receptors on monocytes, thereby
inducing the secretion of inflammatory cytokines (such as IFN-γ and
TNF-α), TF, large amounts of reactive oxygen species, MCP-1,
sFlt-1, PAI-1 and other mediators. This cascade can result in
damage to placental vascular endothelial cells, inhibit the
remodeling of uterine spiral arteries, interfere with normal EVT
invasion, and ultimately lead to abnormal placental development and
fetal loss. APS, antiphospholipid syndrome; aPL, antiphospholipid
antibody; EVT, extravillous trophoblast; IFN, interferon; Th, T
helper; MCP-1, monocyte chemoattractant protein-1; sFlt-1, soluble
fms-like tyrosine kinase-1; PAI-1, plasminogen activator
inhibitor-1; MMP, matrix metalloproteinase; HIF-1,
hypoxia-inducible factor 1.
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Copy and paste a formatted citation
Spandidos Publications style
Huo R, Wei C, Yang Y, Yang Y, Huo X, Wang B, Meng D, Huang Y, Huang R, Lin J, Lin J, et al: Role of monocytes in the pathogenesis of antiphospholipid syndrome and potential therapeutic targets (Review). Mol Med Rep 32: 305, 2025.
APA
Huo, R., Wei, C., Yang, Y., Yang, Y., Huo, X., Wang, B. ... Huang, X. (2025). Role of monocytes in the pathogenesis of antiphospholipid syndrome and potential therapeutic targets (Review). Molecular Medicine Reports, 32, 305. https://doi.org/10.3892/mmr.2025.13670
MLA
Huo, R., Wei, C., Yang, Y., Yang, Y., Huo, X., Wang, B., Meng, D., Huang, Y., Huang, R., Lin, J., Huang, X."Role of monocytes in the pathogenesis of antiphospholipid syndrome and potential therapeutic targets (Review)". Molecular Medicine Reports 32.5 (2025): 305.
Chicago
Huo, R., Wei, C., Yang, Y., Yang, Y., Huo, X., Wang, B., Meng, D., Huang, Y., Huang, R., Lin, J., Huang, X."Role of monocytes in the pathogenesis of antiphospholipid syndrome and potential therapeutic targets (Review)". Molecular Medicine Reports 32, no. 5 (2025): 305. https://doi.org/10.3892/mmr.2025.13670
Copy and paste a formatted citation
x
Spandidos Publications style
Huo R, Wei C, Yang Y, Yang Y, Huo X, Wang B, Meng D, Huang Y, Huang R, Lin J, Lin J, et al: Role of monocytes in the pathogenesis of antiphospholipid syndrome and potential therapeutic targets (Review). Mol Med Rep 32: 305, 2025.
APA
Huo, R., Wei, C., Yang, Y., Yang, Y., Huo, X., Wang, B. ... Huang, X. (2025). Role of monocytes in the pathogenesis of antiphospholipid syndrome and potential therapeutic targets (Review). Molecular Medicine Reports, 32, 305. https://doi.org/10.3892/mmr.2025.13670
MLA
Huo, R., Wei, C., Yang, Y., Yang, Y., Huo, X., Wang, B., Meng, D., Huang, Y., Huang, R., Lin, J., Huang, X."Role of monocytes in the pathogenesis of antiphospholipid syndrome and potential therapeutic targets (Review)". Molecular Medicine Reports 32.5 (2025): 305.
Chicago
Huo, R., Wei, C., Yang, Y., Yang, Y., Huo, X., Wang, B., Meng, D., Huang, Y., Huang, R., Lin, J., Huang, X."Role of monocytes in the pathogenesis of antiphospholipid syndrome and potential therapeutic targets (Review)". Molecular Medicine Reports 32, no. 5 (2025): 305. https://doi.org/10.3892/mmr.2025.13670
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