ArticleBMC medicine2023
Alpha-2-macroglobulin is involved in the occurrence of early-onset pre-eclampsia via its negative impact on uterine spiral artery remodeling and placental angiogenesis.
Article in BMC medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Cell-free DNA fragmentomics for preeclampsia risk assessment.Nature communications · 2026Article
- HIF-1α mediated placental ischemic signaling in the development of early-onset preeclampsia.Redox biology · 2026Review
- Quantitative proteomic profiling of placental extracellular vesicles in recurrent pregnancy loss reveals their role in feto-maternal crosstalk.BMC pregnancy and childbirth · 2026Article
- Ginsenoside Rb1 alleviates endothelial dysfunction and vascular remodeling in preeclampsia via activation of the PI3K-Akt-eNOS pathway.Scientific reports · 2026Article
- Heterochronic changes in gene expression underlie placental evolution in the fish family Poeciliidae.Proceedings. Biological sciences · 2025Article
- SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs.Scientific reports · 2025Article
- Extracellular Vesicles Alter Trophoblast Function in Pregnancies Complicated by COVID-19.Journal of extracellular vesicles · 2025Article
- Targeting A2M-LRP1 reverses uterine spiral artery remodeling disorder and alleviates the progression of preeclampsia.Cell communication and signaling : CCS · 2025Article
- Quercetin alleviates endothelial dysfunction in preeclampsia by inhibiting ferroptosis and inflammation through EGFR binding.Communications biology · 2025Article
- Alpha-2-Macroglobulin and Signature Genes: Predictive Biomarkers for Prognosis and Immunotherapy in Clear Cell Renal Cell Carcinoma.Journal of Cancer · 2025Article
- ITGB3 is reduced in pregnancies with preeclampsia and its influence on biological behavior of trophoblast cells.Molecular medicine (Cambridge, Mass.) · 2024Article
- Preliminary Study on the Positive Expression Regulation of Alpha2-Macroglobulin in the Testicular Tissue of Male Mice by Environmental Estrogens.International journal of molecular sciences · 2024Article
- PPP2R2A inhibition contributes to preeclampsia by regulating the proliferation, apoptosis, and angiogenesis modulation potential of mesenchymal stem cells.Cell division · 2024Article
- [α2-macroglobulin alleviates glucocorticoid-induced avascular necrosis of the femoral head in mice by promoting proliferation, migration and angiogenesis of vascular endothelial cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Quantitative Proteomics of Maternal Blood Plasma in Isolated Intrauterine Growth Restriction.International journal of molecular sciences · 2023Article
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundPre-eclampsia (PE) is one of the leading causes of maternal and fetal morbidity/mortality during pregnancy, and alpha-2-macroglobulin (A2M) is associated with inflammatory signaling; however, the pathophysiological mechanism by which A2M is involved in PE development is not yet understood.
methodsHuman placenta samples, serum, and corresponding clinical data of the participants were collected to study the pathophysiologic mechanism underlying PE. Pregnant Sprague-Dawley rats were intravenously injected with an adenovirus vector carrying A2M via the tail vein on gestational day (GD) 8.5. Human umbilical artery smooth muscle cells (HUASMCs), human umbilical vein endothelial cells (HUVECs), and HTR-8/SVneo cells were transfected with A2M-expressing adenovirus vectors.
resultsIn this study, we demonstrated that A2M levels were significantly increased in PE patient serum, uterine spiral arteries, and feto-placental vasculature. The A2M-overexpression rat model closely mimicked the characteristics of PE (i.e., hypertension in mid-to-late gestation, histological and ultrastructural signs of renal damage, proteinuria, and fetal growth restriction). Compared to the normal group, A2M overexpression significantly enhanced uterine artery vascular resistance and impaired uterine spiral artery remodeling in both pregnant women with early-onset PE and in pregnant rats. We found that A2M overexpression was positively associated with HUASMC proliferation and negatively correlated with cell apoptosis. In addition, the results demonstrated that transforming growth factor beta 1 (TGFβ1) signaling regulated the effects of A2M on vascular muscle cell proliferation described above. Meanwhile, A2M overexpression regressed rat placental vascularization and reduced the expression of angiogenesis-related genes. In addition, A2M overexpression reduced HUVEC migration, filopodia number/length, and tube formation. Furthermore, HIF-1α expression was positively related to A2M, and the secretion of sFLT-1 and PIGF of placental origin was closely related to PE during pregnancy or A2M overexpression in rats.
conclusionsOur data showed that gestational A2M overexpression can be considered a contributing factor leading to PE, causing detective uterine spiral artery remodeling and aberrant placental vascularization.
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