miR-200a as Potential Early-onset Biomarker, while High Nitric Oxide as Potential Late-onset Biomarker in Preeclampsia
Abstract
BACKGROUND: miR-200a is known to alter trophoblast invasion and spiral artery remodeling, leading to defective placentation that causes placental hypoxia, which is the main pathomechanism in early-onset preeclampsia (EOPE). Hypoxic placentas cause systemic endothelial dysfunction that is characterized by low production of endothelial vasodilator, mainly nitric oxide (NO). On the other hand, defective placentation does not cause late-onset preeclampsia (LOPE), making the role of miR-200a expression and NO level as predictors in LOPE questionable. Therefore, this study was conducted to compare miR-200a expressions and NO levels in EOPE and LOPE to clarify their role in pathomechanism of both types of preeclampsia.
METHODS: A cross-sectional comparative study was conducted in 62 preeclamptic patients (31 EOPEs and 31 LOPEs). Subjects were classified into EOPE or LOPE groups based on whether the diagnosis of preeclampsia was made at <34 or ≥34 weeks of pregnancy. miR-200a expression was analyzed using real-time polymerase chain reaction technique, and NO level was analyzed using colorimetric assay method.
RESULTS: EOPE and LOPE subjects were equivalent in terms of age and parity (p=0.709 and p=0.066), but significantly difference in gestational age (p=0.000). miR-200a were expressed in 74.2% of EOPE and 41.9% of LOPE subjects (p=0.010). Median NO levels were lower in EOPE compared to LOPE subjects (23.75 vs. 106.00 µmol/L) (p=0.027), and lower in subjects with detected miR-200a compared to subjects with undetected miR-200a (62.75 vs. 132.25 µmol/L) (p=0.032).
CONCLUSION: miR-200a was more expressed in EOPE compared to LOPE subjects suggesting that it might be a significant in predicting EOPE. While NO level was significantly lower in EOPE whilst higher in LOPE subjects, hence might be potential as a marker to differentiate EOPE and LOPE.
KEYWORDS: miR-200a expression, NO level, early-onset preeclampsia, late-onset preeclampsia
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Ives CW, Sinkey R, Rajapreyar I, Tita ATN, and Oparil S. Preeclampsia - pathophysiology and clinical presentations. J Am Coll Cardiol. 2020; 76(14): 1690-702, CrossRef.
Putri RWR, Prasmusinto D, Wibowo N, Irwinda R, Purwosunu Y, Saroyo YB. Higher trace elements and lower fatty acids levels in erythrocytes as predictors of preeclampsia. Indones Biomed J. 2024; 16(6): 560-71, CrossRef.
Shaw LJ, Patel K, Lala-Trindade A, Feltovich H, Vieira L, Kontorovich A, et al. Pathophysiology of preeclampsia-induced vascular dysfunction and implications for subclinical myocardial damage and heart failure. JACC Adv. 2024; 3(6): 100980, CrossRef.
Kornacki J, Olejniczak O, Sibiak R, Gutaj P, Wender-Ozegowska E. Pathophysiology of pre-eclampsia-two theories of the development of the disease. Int J Mol Sci. 2023; 25(1): 307, CrossRef.
Tomimatsu T, Mimura K, Endo M, Kumasawa K, Kimura T. Pathophysiology of preeclampsia: An angiogenic imbalance and long-lasting systemic vascular dysfunction. Hypertens Res. 2017; 40(4): 305-10, CrossRef.
Burton GJ, Redman CW, Roberts JM, and Moffett A. Pre-eclampsia: Pathophysiology and clinical implications. BMJ. 2019; 366: l2381, CrossRef.
Giannubilo SR, Cecati M, Marzioni D, Ciavattini A. Circulating miRNAs and preeclampsia: From implantation to epigenetics. Int J Mol Sci. 2024; 25(3):1418, CrossRef.
Sumawan H, Giantari I, Mubarika S, Hadiati DR, Pradjatmo H. Exosomal miRNAs as potential biomarkers for preeclampsia: miR-1283 has the highest expression, while miR-152-3p has the lowest expression. Indones Biomed J. 2024; 16(4): 387-96, CrossRef.
Nelson N, Yusrawati, Serudji J, Jamsari, Amir A, Afriwardi, et al. Elevation of miR-210 expression and mean arterial pressure as early-onset pre-eclampsia biomarkers, while elevation of matrix metalloproteinase-2 as late-onset pre-eclampsia biomarker. Indones Biomed J. 2025; 17(2): 180-7, CrossRef.
He X, Ding D. High miR-200a-3p expression has high diagnostic values for hypertensive disorders complicating pregnancy and predicts adverse pregnancy outcomes. BMC Pregnancy Childbirth. 2022; 22(1): 490, CrossRef.
Wang C, Tsai P, Chen T, Tsai H, Kuo P, Su M. Elevated miR-200a and miR-141 inhibit endocrine gland-derived vascular endothelial growth factor expression and ciliogenesis in preeclampsia. J Physiol. 2019; 597(12): 3069-83, CrossRef.
Wu G, Jin Y, Cao Y, Li J. The diagnostic value and regulatory mechanism of miR-200a targeting ZEB1 in pregnancy-induced hypertension. Hypertens Pregnancy. 2020; 39(3): 243-51, CrossRef.
Nemecz M, Alexandru N, Tanko G. Role of microRNA in endothelial dysfunction and hypertension. Curr Hypertens Rep. 2016; 18(12): 87, CrossRef.
Redman CW. Early and late onset preeclampsia: Two sides of the same coin. Hypertens Pregnancy. 2017; 7: 58, CrossRef.
Shi C, Yang Y, Zhang L, Yu J, Qin S, Xu H, Gao Y. MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9. Onco Targets Ther. 2019; 12: 8329-38, CrossRef.
Su MT, Tsai PY, Wang CY, Tsai HL, Kuo PL. Aspirin facilitates trophoblast invasion and epithelial-mesenchymal transition by regulating the miR-200-ZEB1 axis in preeclampsia. Biomed Pharmacother. 2021; 139: 111591, CrossRef.
Saha S, Choudhury J, Ain R. MicroRNA-141-3p and miR-200a-3p regulate insulin-like growth factor 2 during mouse placental development. Mol Cell Endocrinol. 2015: 414: 186-93, CrossRef.
Puspasari A, Enis RN, Herlambang. Genetic variant of vascular endothelial growth factor (VEGF)-A rs699947 is associated with preeclampsia. Mol Cell Biomed Sci. 2022; 6(2): 70-6, CrossRef.
Serudji J, Basyir V, Fadhillah T. Differentiating material angiogenesis factors between early and late onset preeclampsia: Higher sFlt-1 in early onset preclampsia, lower PlGF and higher sFlt-1/PlGF ratio in late-onset preeclampsia. Mol Cell Biomed Sci. 2024; 8(3): 154-58, CrossRef.
Staff AC. The two-stage placental model of preeclampsia: An update. J Reprod Immunol. 2019; 134-135: 1-10, CrossRef.
Hodzic J, Izetbegivic S, Muracevic B, Iriskic R, Jovic HS. Nitric oxide biosynthesis during normal pregnancy and pregnancy complicated by preeclampsia. Med Glas. 2017; 14(2): 211-7, CrossRef.
Degjoni A, Campolo F, Stefanini L, Venneri MA. The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders. J Thromb Haemost. 2022; 20(11): 2465-74, CrossRef.
Pan F, Qiu X, Yu W, Zhang Q, Chen Q, Zhang C, et al. MicroRNA‑200a is up‑regulated in aged rats with erectile dysfunction and could attenuate endothelial function via SIRT1 inhibition. Asian J Androl. 2016; 18(1): 74-9, CrossRef.
Daiber A, Xia N, Steven S, Oelze M, Hanf A, Kröller-Schön S, et al. New therapeutic implications of endothelial nitric oxide synthase (eNOS) function/dysfunction in cardiovascular disease. Int J Mol Sci. 2019; 20(1): 187, CrossRef.
Theofilis P, Sagris M, Oikonomou E, Antonopoulos AS, Siasos G, Tsioufis C, et al. Inflammatory mechanisms contributing to endothelial dysfunction. Biomedicines. 2021; 9(7): 781, CrossRef.
Cyr AR, Huckaby LV, Shiva SS, Zuckerbraun BS. Nitric oxide and endothelial dysfunction. Crit Care Clin. 2020; 36(2): 307-21, CrossRef.
Duckles SP, Miller VM. Hormonal modulation of endothelial NO production. Pflugers Arch. 2010; 459(6): 841-51, CrossRef.
Nava E, Llorens S. The local regulation of vascular function: From an inside-outside to an outside-inside model. Front Physiol. 2019; 10: 729, CrossRef.
DOI: https://doi.org/10.18585/inabj.v17i3.3572
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