Sameera Dabbiru

Background: Pre-eclampsia is a systemic condition of hypertension and proteinuria during pregnancy that primarily involves placental dysfunction.¹ A diagnosis requires a recurrent blood pressure greater than 140/90 mmHg and greater than 300 mg proteinuria sample.^2,3 The disease is characterized by limited placenta perfusion due to damaged spiral arteries and an imbalance of angiogenic factors, resulting in a state of inflammation and vascular disruption.¹ There are currently no treatments, so the focus for researchers has shifted to identifying biomarkers for potential therapeutic targets.¹ Biomarkers that interact with angiogenic factor VEGF, such as the long noncoding RNA MALAT-1, have been identified as potential points of interest.⁴

Objectives: In this narrative review, we explore potential biomarkers of pre-eclampsia, as well as potential therapeutic targets.

Search Methods: An online search  in the PubMed database was conducted from 2018 to 2026 using the following keywords: “pre-eclampsia”, “VEGF”, “MALAT1”

Results: Plasma samples from pre-eclamptic patients indicated that lncRNA MALAT1 was especially upregulated and blocked miRNA function in patients with pre-eclampsia.⁵ Additionally, knockout MALAT1 assays indicated a reduction of trophoblastic proliferation and invasion, as well as increased trophoblastic apoptosis. ⁴ In order to identify MALAT1’s relationship with angiogenesis, levels of VEGF were also observed – notable downregulation indicated weakened spiral artery remodeling.⁴ CORO1C is another protein that works to promote tumor proliferation and low levels in pre-eclamptic patients indicated reduced migration and proliferation of placental cells and correlated with low MALAT1.⁶ To improve pre-eclampsia diagnosis, a clinical trial was conducted to see if PIGF values, another angiogenetic factor similar to VEGF, can decrease the time it takes for physicians to make a pre-eclampsia diagnosis.⁷ Using a cluster model, the trial concluded by quantifying that the time for diagnosis was 4·1 days in the unrevealed group and 1·9 days for the group with exposed PIGF values, indicating a shorter time for an accurate pre-eclampsia diagnosis.⁷ To better explore treatments, a double blind and placebo controlled study observed that patients on metformin had an extended gestational time of an additional week.⁸ It concluded that extended release metformin could be a potential therapeutic agent that can prolong gestation and thus improve health outcomes of both the mother and fetus for pre-term pre-eclampsia cases.⁸

Conclusion: The need for improved diagnostics and treatments for pre-eclampsia continues to make it a highly researched disease. lncRNA MALAT1 is reduced and is thus correlated with the diminished placental growth and trophoblastic invasion seen in pre-eclamptic patients.⁴ The impact of MALAT1 is further amplified by down regulation of VEGF and CORO1C, as they deteriorate spiral artery health in the placenta.^{4, 6} In terms of improving diagnostic conditions, PIGF levels helped physicians provide more focused care and improved maternal and fetal outcomes.⁷ While no treatment exists for pre-eclampsia, extended release metformin was able to target a specific part of the pathogenesis by prolonging gestational times for pre-term pre-eclampsic mothers.⁸

Works Cited:

1. Chappell LC, Cluver CA, Kingdom J, Tong S. Pre-eclampsia. The Lancet. 2021;398(10297):341-354. doi:10.1016/S0140-6736(20)32335-7
2. Khosla K, Jin Y, Espinoza J, et al. Signs or symptoms of suspected preeclampsia – A retrospective national database study of prevalence, costs, and outcomes. Pregnancy Hypertension. 2024/06/01/ 2024;36:101124. doi:https://doi.org/10.1016/j.preghy.2024.101124
3. Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. May 2019;15(5):275-289. doi:10.1038/s41581-019-0119-6
4. Feng C, Cheng L, Jin J, Liu X, Wang F. Long non-coding RNA MALAT1 regulates trophoblast functions through VEGF/VEGFR1 signaling pathway. Archives of Gynecology and Obstetrics. 2021/10/01 2021;304(4):873-882. doi:10.1007/s00404-021-05987-y
5. Zhou S, Li J, Yang W, et al. Noninvasive preeclampsia prediction using plasma cell–free RNA signatures. American Journal of Obstetrics and Gynecology. 2023/11/01/ 2023;229(5):553.e1-553.e16. doi:https://doi.org/10.1016/j.ajog.2023.05.015
6. Nie H, Wang X, Dong X, et al. Down-regulation of CORO1C mediated by lncMALAT1/miR-133a-3p axis contributes to trophoblast dysfunction and preeclampsia. Placenta. 2024/10/01/ 2024;156:67-76. doi:https://doi.org/10.1016/j.placenta.2024.09.007
7. Duhig KE, Myers J, Seed PT, et al. Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial. Lancet. May 4 2019;393(10183):1807-1818. doi:10.1016/s0140-6736(18)33212-4
8. Cluver CA, Hiscock R, Decloedt EH, et al. Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial. Bmj. Sep 22 2021;374:n2103. doi:10.1136/bmj.n2103