Effect of hydroxychloroquine on antiphospholipid antibodies-inhibited endometrial angiogenesis

Abstract

Background

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic events and/or pregnancy morbidity (≥3 recurrent early miscarriage or fetal death or a prematurity <34 weeks of gestation) with persistently positive antiphospholipid antibodies (aPLs). It is reported that aPLs damage the placental tissue by binding to β2-glycoprotein I (β2GPI) on the surface of trophoblast and endothelial cells. Hydroxychloroquine (HCQ) is considered to be beneficial in the treatment of obstetrical APS and shown to restore the aPL-inhibited invasion and differentiation of trophoblast. However, not enough evidence exists regarding the effect of HCQ on endometrial angiogenesis. The aim of our study was to assess whether HCQ has an effect on aPL-inhibited endothelial angiogenesis.

Methods

In this research, to explore the effect of HCQ for angiogenesis, we investigated: (1) Human umbilical vein endothelial cells (HUVECs) viability by CCK-8; (2) HUVECs migration by wound healing; (3) HUVEC angiogenesis by Matrigel assay in vitro; (4) mRNA expression of MMP-2 and VEGF by real-time quantitative Polymerase Chain Reaction (RT-PCR); (5) protein expression of VEGF, MMP-2 by western blot.

Results

We found that HCQ treatment significantly restored the expression of aPL-inhibited VEGF and MMP-2. HCQ restored aPL-inhibited HUVEC proliferation, migration, and angiogenesis in vitro.

Conclusion

In conclusion, aPLs inhibit HUVECs angiogenesis, however, HCQ can restore the effect of aPL-inhibited HUVECs migration and angiogenesis in vitro, demonstrating its beneficial therapeutic role in obstetrical APS.

Keywords:

• Obstetric antiphospholipid syndrome
• antiphospholipid antibodies
• hydroxychloroquine
• angiogenesis

Acknowledgements

All authors would like to thank the women who donated tissue for this study.

Ethics approval and consent to participant

The study design as well as the experimental methods used in the current study were approved by the Institutional Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong University. All participants signed informed consent forms.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used during the present study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was funded by the National Natural Science Foundation of China [81873842 and 81571461].