Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Low-dose Aspirin may Prevent Preeclampsia by Inhibiting the Expression of ATF2

Author(s): Sha Xiao, Lu Guo, Ming Zhang, Rong Hu and Rong Liu*

Volume 23, Issue 5, 2023

Published on: 28 December, 2022

Page: [702 - 710] Pages: 9

DOI: 10.2174/1871530323666221103105349

Price: $65

Abstract

Aims: To explore the ATF2 expression of preeclampsia patients and investigate whether the level of ATF2 expression impacted the low-dose aspirin treatment of preeclampsia patients.

Background: Preeclampsia is a severe pregnancy-related hypertension disorder and refers to hypertension.

Objective: This study was designed to explore the activating transcription factor 2 (ATF2) expression of preeclampsia patients and investigate whether the level of ATF2 expression impacted the low-dose aspirin treatment of preeclampsia patients.

Methods: Firstly, we collected the plasma of normal and preeclampsia pregnancies and quantified the expressions of ATF2 by ELISA. Then we quantified the expression of the three downstream target genes of ATF2 (IL-8, IL-6 and MMP-2). Finally, we collected and quantified the interventional and observational group plasma. All data were compared by t-test (p<0.05).

Results: ATF2 and its target genes (IL-6, IL-8 and MMP-2) were upregulated in preeclampsia patients. In addition, ATF2 and its target genes were downregulated in the interventional group (LDA-treated group).

Conclusion: Our results indicated that LDA could inhibit ATF2 expression in preeclampsia. It suggests that ATF2 may be a potential target of LDA in the prevention of preeclampsia.

Keywords: Congenital adrenal hyperplasia, 11-beta hydroxylase deficiency, 11-deoxycortysol, CYP11B1 gene, mineralocorticoid pressure levels, ATF2.

Graphical Abstract
[1]
Rana, S.; Lemoine, E.; Granger, J.P.; Karumanchi, S.A. Preeclampsia. Circ. Res., 2019, 124(7), 1094-1112.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.313276] [PMID: 30920918]
[2]
Sibai, B.M.; Stella, C.L. Diagnosis and management of atypical preeclampsia-eclampsia. Am. J. Obstet. Gynecol., 2009, 200(5), 481.
[http://dx.doi.org/10.1016/j.ajog.2008.07.048]
[3]
Xiao, S.; Zhang, Q.; Zhang, M.; Hu, R.; Liu, R. A modified Mediterranean diet against gestational diabetes mellitus. STE Med., 2022, 3(3), e129.
[http://dx.doi.org/10.37175/stemedicine.v3i3.129]
[4]
Uzan, J.; Carbonnel, M.; Piconne, O.; Asmar, R.; Ayoubi, J.M. Preeclampsia: Pathophysiology, diagnosis, and management. Vasc. Health Risk Manag., 2011, 7, 467-474.
[PMID: 21822394]
[5]
Collier, A.Y.; Smith, L.A.; Karumanchi, S.A. Review of the immune mechanisms of preeclampsia and the potential of immune modulating therapy. Hum. Immunol., 2021, 82(5), 362-370.
[http://dx.doi.org/10.1016/j.humimm.2021.01.004] [PMID: 33551128]
[6]
Atallah, A.; Lecarpentier, E.; Goffinet, F.; Doret, D.M.; Gaucherand, P.; Tsatsaris, V. Aspirin for prevention of preeclampsia. Drugs, 2017, 77(17), 1819-1831.
[http://dx.doi.org/10.1007/s40265-017-0823-0] [PMID: 29039130]
[7]
Jim, B.; Karumanchi, S.A. Preeclampsia: Pathogenesis, prevention, and long-term complications. Semin. Nephrol., 2017, 37(4), 386-397.
[http://dx.doi.org/10.1016/j.semnephrol.2017.05.011] [PMID: 28711078]
[8]
Roberge, S.; Nicolaides, K.H.; Demers, S.; Villa, P.; Bujold, E. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: A meta-analysis. Ultrasound Obstet. Gynecol., 2013, 41(5), 491-499.
[http://dx.doi.org/10.1002/uog.12421] [PMID: 23362106]
[9]
Wang, Y.; Cheng, K.; Zhou, W.; Liu, H.; Yang, T.; Hou, P.; Li, X. miR-141-5p regulate ATF2 via effecting MAPK1/ERK2 signaling to promote preeclampsia. Biomed. Pharmacother., 2019, 115, 108953.
[http://dx.doi.org/10.1016/j.biopha.2019.108953] [PMID: 31075732]
[10]
Watson, G.; Ronai, Z.A.; Lau, E. ATF2, a paradigm of the multifaceted regulation of transcription factors in biology and disease. Pharmacol. Res., 2017, 119, 347-357.
[http://dx.doi.org/10.1016/j.phrs.2017.02.004] [PMID: 28212892]
[11]
Feng, Y.L.; Yin, Y.X.; Ding, J.; Yuan, H.; Yang, L.; Xu, J.J.; Hu, L.Q. Alpha-1-antitrypsin suppresses oxidative stress in preeclampsia by inhibiting the p38MAPK signaling pathway: An in vivo and in vitro study. PLoS One, 2017, 12(3), e0173711.
[http://dx.doi.org/10.1371/journal.pone.0173711] [PMID: 28358847]
[12]
Yu, T.; Li, Y.J.; Bian, A.H.; Zuo, H.B.; Zhu, T.W.; Ji, S.X.; Kong, F.; Yin, D.Q.; Wang, C.B.; Wang, Z.F.; Wang, H.Q.; Yang, Y.; Yoo, B.C.; Cho, J.Y. The regulatory role of activating transcription factor 2 in inflammation. Mediators Inflamm., 2014, 2014, 950472.
[http://dx.doi.org/10.1155/2014/950472] [PMID: 25049453]
[13]
Lopez, B.P.; Lau, E.; Ronai, Z. Emerging roles of ATF2 and the dynamic AP1 network in cancer. Nat. Rev. Cancer, 2010, 10(1), 65-76.
[http://dx.doi.org/10.1038/nrc2681] [PMID: 20029425]
[14]
Szabo, S.; Mody, M.; Romero, R.; Xu, Y.; Karaszi, K.; Mihalik, N.; Xu, Z.; Bhatti, G.; Fule, T.; Hupuczi, P.; Krenacs, T.; Rigo, J., Jr; Tarca, A.L.; Hassan, S.S.; Chaiworapongsa, T.; Kovalszky, I.; Papp, Z.; Than, N.G. Activation of villous trophoblastic p38 and ERK1/2 signaling pathways in preterm preeclampsia and HELLP syndrome. Pathol. Oncol. Res., 2015, 21(3), 659-668.
[http://dx.doi.org/10.1007/s12253-014-9872-9] [PMID: 25583406]
[15]
Vaillancourt, C.; Lanoix, D.; Le Bellego, F.; Daoud, G.; Lafond, J. Involvement of MAPK signalling in human villous trophoblast differentiation. Mini Rev. Med. Chem., 2009, 9(8), 962-973.
[http://dx.doi.org/10.2174/138955709788681663] [PMID: 19601892]
[16]
D’Oria, R.; Laviola, L.; Giorgino, F.; Unfer, V.; Bettocchi, S.; Scioscia, M. PKB/Akt and MAPK/ERK phosphorylation is highly induced by inositols: Novel potential insights in endothelial dysfunction in preeclampsia. Pregnancy Hypertens., 2017, 10, 107-112.
[http://dx.doi.org/10.1016/j.preghy.2017.07.001] [PMID: 29153661]
[17]
Tranquilli, A.L. Introduction to ISSHP new classification of preeclampsia. Pregnancy Hypertens., 2013, 3(2), 58-59.
[http://dx.doi.org/10.1016/j.preghy.2013.04.006] [PMID: 26105838]
[18]
Park, F.J.; Leung, C.H.Y.; Poon, L.C.Y.; Williams, P.F.; Rothwell, S.J.; Hyett, J.A. Clinical evaluation of a first trimester algorithm predicting the risk of hypertensive disease of pregnancy. Aust. N. Z. J. Obstet. Gynaecol., 2013, 53(6), 532-539.
[http://dx.doi.org/10.1111/ajo.12126] [PMID: 23919594]
[19]
El-Achi, V.; Park, F.; O’Brien, C.; Tooher, J.; Hyett, J. Does low dose aspirin prescribed for risk of early onset preeclampsia reduce the prevalence of preterm prelabor rupture of membranes? J. Matern. Fetal Neonatal Med., 2021, 34(4), 618-623.
[http://dx.doi.org/10.1080/14767058.2019.1611768] [PMID: 31018725]
[20]
Khong, T.Y.; Wolf, F.; Robertson, W.B.; Brosens, I. Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. BJOG, 1986, 93(10), 1049-1059.
[http://dx.doi.org/10.1111/j.1471-0528.1986.tb07830.x] [PMID: 3790464]
[21]
Song, H.; Ki, S.H.; Kim, S.G.; Moon, A. Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells. Cancer Res., 2006, 66(21), 10487-10496.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1461] [PMID: 17079470]
[22]
Franchimont, N.; Durant, D.; Rydziel, S.; Canalis, E. Platelet-derived growth factor induces interleukin-6 transcription in osteoblasts through the activator protein-1 complex and activating transcription factor-2. J. Biol. Chem., 1999, 274(10), 6783-6789.
[http://dx.doi.org/10.1074/jbc.274.10.6783] [PMID: 10037779]
[23]
Hisatsune, J.; Nakayama, M.; Isomoto, H.; Kurazono, H.; Mukaida, N.; Mukhopadhyay, A.K.; Azuma, T.; Yamaoka, Y.; Sap, J.; Yamasaki, E.; Yahiro, K.; Moss, J.; Hirayama, T. Molecular characterization of Helicobacter pylori VacA induction of IL-8 in U937 cells reveals a prominent role for p38MAPK in activating transcription factor-2, cAMP response element binding protein, and NF-kappaB activation. J. Immunol., 2008, 180(7), 5017-5027.
[http://dx.doi.org/10.4049/jimmunol.180.7.5017] [PMID: 18354227]
[24]
Aggarwal, R.; Jain, A.K.; Mittal, P.; Kohli, M.; Jawanjal, P.; Rath, G. Association of pro- and anti-inflammatory cytokines in preeclampsia. J. Clin. Lab. Anal., 2019, 33(4), e22834.
[http://dx.doi.org/10.1002/jcla.22834] [PMID: 30666720]
[25]
Timokhina, E.; Strizhakov, A.; Ibragimova, S.; Gitel, E.; Ignatko, I.; Belousova, V.; Zafiridi, N. Matrix metalloproteinases MMP-2 and MMP-9 occupy a new role in severe preeclampsia. J. Pregnancy, 2020, 2020, 8369645.
[http://dx.doi.org/10.1155/2020/8369645] [PMID: 33381317]
[26]
Sun, L.; Mao, D.; Cai, Y.; Tan, W.; Hao, Y.; Li, L.; Liu, W. Association between higher expression of Interleukin-8 (IL-8) and haplotype−353A/−251A/+678T of IL-8 gene with preeclampsia. Medicine, 2016, 95(52), e5537.
[http://dx.doi.org/10.1097/MD.0000000000005537] [PMID: 28033248]
[27]
Bujold, E.; Roberge, S.; Lacasse, Y.; Bureau, M.; Audibert, F.; Marcoux, S.; Forest, J.C.; Giguère, Y. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: A meta-analysis. Obstet. Gynecol., 2010, 116(2), 402-414.
[http://dx.doi.org/10.1097/AOG.0b013e3181e9322a] [PMID: 20664402]
[28]
Redman, C.W.; Bonnar, J.; Beilin, L. Early platelet consumption in pre-eclampsia. BMJ, 1978, 1(6111), 467-469.
[http://dx.doi.org/10.1136/bmj.1.6111.467] [PMID: 626836]
[29]
Janes, S.L.; Kyle, P.M.; Redman, C.; Goodall, A.H. Flow cytometric detection of activated platelets in pregnant women prior to the development of pre-eclampsia. Thromb. Haemost., 1995, 74(4), 1059-1063.
[http://dx.doi.org/10.1055/s-0038-1649882] [PMID: 8560414]
[30]
Thorp, J.A.; Walsh, S.W.; Brath, P.C. Low-dose aspirin inhibits thromboxane, but not prostacyclin, production by human placental arteries. Am. J. Obstet. Gynecol., 1988, 159(6), 1381-1384.
[http://dx.doi.org/10.1016/0002-9378(88)90560-1] [PMID: 3061295]
[31]
Cindrova, D.T.; Spasic, B.O.; Jauniaux, E.; Charnock, J.D.S.; Burton, G.J. Nuclear factor-κ B, p38, and stress-activated protein kinase mitogen-activated protein kinase signaling pathways regulate proinflammatory cytokines and apoptosis in human placental explants in response to oxidative stress: Effects of antioxidant vitamins. Am. J. Pathol., 2007, 170(5), 1511-1520.
[http://dx.doi.org/10.2353/ajpath.2007.061035] [PMID: 17456758]
[32]
Roberts, J.M.; Hubel, C.A. Is oxidative stress the link in the two-stage model of pre-eclampsia? Lancet, 1999, 354(9181), 788-789.
[http://dx.doi.org/10.1016/S0140-6736(99)80002-6] [PMID: 10485715]
[33]
Raghupathy, R.; Al-Azemi, M.; Azizieh, F. Intrauterine growth restriction: Cytokine profiles of trophoblast antigen-stimulated maternal lymphocytes. Clin. Dev. Immunol., 2012, 2012, 1-10.
[http://dx.doi.org/10.1155/2012/734865] [PMID: 22110537]
[34]
Redman, C.W.G.; Sargent, I.L. Pre-eclampsia, the placenta and the maternal systemic inflammatory response - A review. Placenta, 2003, 24(Suppl. A), S21-S27.
[http://dx.doi.org/10.1053/plac.2002.0930] [PMID: 12842410]
[35]
Koch, A.E.; Polverini, P.J.; Kunkel, S.L.; Harlow, L.A.; DiPietro, L.A.; Elner, V.M.; Elner, S.G.; Strieter, R.M. Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science, 1992, 258(5089), 1798-1801.
[http://dx.doi.org/10.1126/science.1281554] [PMID: 1281554]
[36]
Robinson, K.F.; Narasipura, S.D.; Wallace, J.; Ritz, E.M.; Al-Harthi, L. Negative regulation of IL-8 in human astrocytes depends on β-catenin while positive regulation is mediated by TCFs/LEF/ATF2 interaction. Cytokine, 2020, 136, 155252.
[http://dx.doi.org/10.1016/j.cyto.2020.155252] [PMID: 32818703]
[37]
Nugent, W.H.; Mishra, N.; Strauss, J.F., III; Walsh, S.W. Matrix metalloproteinase 1 causes vasoconstriction and enhances vessel reactivity to angiotensin II via protease-activated receptor 1. Reprod. Sci., 2016, 23(4), 542-548.
[http://dx.doi.org/10.1177/1933719115607998] [PMID: 26438597]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy