Serum kallistatin level is decreased in women with preeclampsia

Onur Güralp 1 , Nevin Tüten 2 , Koray Gök 3 , Kübra Hamzaoglu 4 , Huri Bulut 5 , Meike Schild-Suhren 1 , Eduard Malik 1 , and Abdullah Tüten 4
  • 1 Carl von Ossietzky Oldenburg University, University Hospital for Gynecology and Obstetrics, Klinikum Oldenburg AöR, Oldenburg, Germany
  • 2 Obstetrics and Gynecology, Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey
  • 3 Obstetrics and Gynecology, Sakarya University, Education and Research Hospital, Sakarya, Turkey
  • 4 Department of Obstetrics and Gynecology, Istanbul Cerrahpasa University, Istanbul, Turkey
  • 5 Medical Biochemistry Department, Istinye University, Faculty of Medicine, Istanbul, Turkey
Onur Güralp
  • Corresponding author
  • Carl von Ossietzky Oldenburg University, University Hospital for Gynecology and Obstetrics, Klinikum Oldenburg AöR, Oldenburg, Germany
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, Nevin Tüten
  • Obstetrics and Gynecology, Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey
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, Koray Gök
  • Obstetrics and Gynecology, Sakarya University, Education and Research Hospital, Sakarya, Turkey
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, Kübra Hamzaoglu
  • Department of Obstetrics and Gynecology, Istanbul Cerrahpasa University, Istanbul, Turkey
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, Huri Bulut
  • Medical Biochemistry Department, Istinye University, Faculty of Medicine, Istanbul, Turkey
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, Meike Schild-Suhren
  • Carl von Ossietzky Oldenburg University, University Hospital for Gynecology and Obstetrics, Klinikum Oldenburg AöR, Oldenburg, Germany
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, Eduard Malik
  • Carl von Ossietzky Oldenburg University, University Hospital for Gynecology and Obstetrics, Klinikum Oldenburg AöR, Oldenburg, Germany
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and Abdullah Tüten
  • Department of Obstetrics and Gynecology, Istanbul Cerrahpasa University, Istanbul, Turkey
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Abstract

Objectives

To evaluate the serum levels of the serine proteinase inhibitor kallistatin in women with preeclampsia (PE).

Methods

The clinical and laboratory parameters of 55 consecutive women with early-onset PE (EOPE) and 55 consecutive women with late-onset PE (LOPE) were compared with 110 consecutive gestational age (GA)-matched (±1 week) pregnant women with an uncomplicated pregnancy and an appropriate for gestational age fetus.

Results

Mean serum kallistatin was significantly lower in women with PE compared to the GA-matched-controls (27.74±8.29 ng/mL vs. 37.86±20.64 ng/mL, p<0.001); in women with EOPE compared to that of women in the control group GA-matched for EOPE (24.85±6.65 ng/mL vs. 33.37±17.46 ng/mL, p=0.002); and in women with LOPE compared to that of women in the control group GA-matched for LOPE (30.87±8.81 ng/mL vs. 42.25±22.67 ng/mL, p=0.002). Mean serum kallistatin was significantly lower in women with EOPE compared to LOPE (24.85±6.65 ng/mL vs. 30.87±8.81 ng/mL, p<0.001). Serum kallistatin had negative correlations with systolic and diastolic blood pressure, creatinine, and positive correlation with GA at sampling and GA at birth.

Conclusions

Serum kallistatin levels are decreased in preeclamptic pregnancies compared to the GA-matched-controls. This decrease was also significant in women with EOPE compared to LOPE. Serum kallistatin had negative correlation with systolic and diastolic blood pressure, creatinine and positive correlation with GA at sampling and GA at birth.

  • 1.

    Poon, LC, Shennan, A, Hyett, JA, Kapur, A, Hadar, E, Divakar, H, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: a pragmatic guide for first-trimester screening and prevention. Int J Gynaecol Obstet 2019;145:1–33.https://doi.org/10.1002/ijgo.12802.

    • Crossref
    • PubMed
    • Export Citation
  • 2.

    Sutton, EF, Gemmel, M, Powers, RW. Nitric oxide signaling in pregnancy and preeclampsia. Nitric Oxide 2020;95:55–62.https://doi.org/10.1016/j.niox.2019.11.006.

    • Crossref
    • PubMed
    • Export Citation
  • 3.

    Chao, J, Chai, KX, Chen, LM, Xiong, W, Chao, S, Woodley-Miller, C, et al. Tissue kallikrein-binding protein is a serpin. I. Purification, characterization, and distribution in normotensive and spontaneously hypertensive rats. J Biol Chem 1990;265:16394–401.

    • PubMed
    • Export Citation
  • 4.

    Chen, VC, Chao, L, Chao, J. Reactive-site specificity of human kallistatin toward tissue kallikrein probed by site-directed mutagenesis. Biochim Biophys Acta 2000;1479:237–46. https://doi.org/10.1016/s0167-4838(00)00044-3.

    • Crossref
    • PubMed
    • Export Citation
  • 5.

    Chen, VC, Chao, L, Chao, J. Roles of the P1, P2, and P3 residues in determining inhibitory specificity of kallistatin toward human tissue kallikrein. J Biol Chem 2000;275:38457–66.https://doi.org/10.1074/jbc.m005605200.

    • Crossref
    • PubMed
    • Export Citation
  • 6.

    Chen, VC, Chao, L, Pimenta, DC, Bledsoe, G, Juliano, L, Chao, J. Identification of a major heparin-binding site in kallistatin. J Biol Chem 2001;276:1276–84.https://doi.org/10.1074/jbc.m005791200.

    • Crossref
    • Export Citation
  • 7.

    Chao, J, Bledsoe, G, Chao, L. Protective role of kallistatin in vascular and organ injury. Hypertension 2016;68:533–41.https://doi.org/10.1161/hypertensionaha.116.07861.

    • Crossref
    • PubMed
    • Export Citation
  • 8.

    Chao, J, Chao, L. Biochemistry, regulation and potential function of kallistatin. Biol Chem Hoppe Seyler 1995;376:705–13.

    • PubMed
    • Export Citation
  • 9.

    Chen, LM, Song, Q, Chao, L, Chao, J. Cellular localization of tissue kallikrein and kallistatin mRNAs in human kidney. Kidney Int 1995;48:690–7.https://doi.org/10.1038/ki.1995.339.

    • Crossref
    • PubMed
    • Export Citation
  • 10.

    Wolf, WC, Harley, RA, Sluce, D, Chao, L, Chao, J. Localization and expression of tissue kallikrein and kallistatin in human blood vessels. J Histochem Cytochem 1999;47:221–8.https://doi.org/10.1177/002215549904700210.

    • Crossref
    • PubMed
    • Export Citation
  • 11.

    Miao, RQ, Agata, J, Chao, L, Chao, J. Kallistatin is a new inhibitor of angiogenesis and tumor growth. Blood 2002;100:3245–52.https://doi.org/10.1182/blood-2002-01-0185.

    • Crossref
    • PubMed
    • Export Citation
  • 12.

    Chao, J, Miao, RQ, Chen, V, Chen, LM, Chao, L. Novel roles of kallistatin, a specific tissue kallikrein inhibitor, in vascular remodeling. Biol Chem 2001;382:15–21.https://doi.org/10.1515/bc.2001.003.

    • PubMed
    • Export Citation
  • 13.

    Gao, L, Yin, H, Smith R J, S., Chao, L, Chao, J. Role of kallistatin in prevention of cardiac remodeling after chronic myocardial infarction. Lab Invest 2008;88:1157–66.https://doi.org/10.1038/labinvest.2008.85.

    • Crossref
    • PubMed
    • Export Citation
  • 14.

    Lin, WC, Chen, CW, Huang, YW, Chao, L, Chao, J, Lin, YS, et al. Kallistatin protects against sepsis-related acute lung injury via inhibiting inflammation and apoptosis. Sci Rep 2015;5:12463.https://doi.org/10.1038/srep12463.

    • Crossref
    • PubMed
    • Export Citation
  • 15.

    Chao, J, Schmaier, A, Chen, LM, Yang, Z, Kallistatin, CL. A novel human tissue kallikrein inhibitor: levels in body fluids, blood cells, and tissues in health and disease. J Lab Clin Med 1996;127:612–20.https://doi.org/10.1016/s0022-2143(96)90152-3.

    • Crossref
    • PubMed
    • Export Citation
  • 16.

    Stadnicki, A, Mazurek, U, Plewka, D, Wilczok, T. Intestinal tissue kallikrein-kallistatin profile in inflammatory bowel disease. Int Immunopharmacol 2003;3:939–44.https://doi.org/10.1016/s1567-5769(03)00054-7.

    • Crossref
    • PubMed
    • Export Citation
  • 17.

    Cheng, Z, Lv, Y, Pang, S, Bai, R, Wang, M, Lin, S, et al. Kallistatin, a new and reliable biomarker for the diagnosis of liver cirrhosis. Acta Pharm Sin B 2015;5:194–200.https://doi.org/10.1016/j.apsb.2015.02.003.

    • Crossref
    • Export Citation
  • 18.

    Lin, WC, Lu, SL, Lin, CF, Chen, CW, Chao, L, Chao, J, et al. Plasma kallistatin levels in patients with severe community-acquired pneumonia. Crit Care 2013;17:R27.https://doi.org/10.1186/cc12507.

    • Crossref
    • PubMed
    • Export Citation
  • 19.

    Zhu, H, Chao, J, Kotak, I, Guo, D, Parikh, SJ, Bhagatwala, J, et al. Plasma kallistatin is associated with adiposity and cardiometabolic risk in apparently healthy African American adolescents. Metabolism 2013;62:642–6.https://doi.org/10.1016/j.metabol.2012.10.012.

    • Crossref
    • PubMed
    • Export Citation
  • 20.

    Maul, H, Longo, M, Saade, GR, Garfield, RE. Nitric oxide and its role during pregnancy: from ovulation to delivery. Curr Pharm Des 2003;9:359–80.https://doi.org/10.2174/1381612033391784.

    • Crossref
    • PubMed
    • Export Citation
  • 21.

    Zullino, S, Buzzella, F, Simoncini, T. Nitric oxide and the biology of pregnancy. Vasc Pharmacol 2018;110:71–4.https://doi.org/10.1016/j.vph.2018.07.004.

    • Crossref
    • Export Citation
  • 22.

    Schleussner, E, Lehmann, T, Kahler, C, Schneider, U, Schlembach, D, Groten, T. Impact of the nitric oxide-donor pentaerythrityl-tetranitrate on perinatal outcome in risk pregnancies: a prospective, randomized, double-blinded trial. J Perinat Med 2014;42:507–14.https://doi.org/10.1515/jpm-2013-0212.

    • PubMed
    • Export Citation
  • 23.

    Schleussner, E, Lehmann, T, Kahler, C, Schneider, U, Schlembach, D, Groten, T. Erratum to: impact of the nitric oxide-donor pentaerythrityl-tetranitrate on perinatal outcome in risk pregnancies: a prospective, randomized, double-blinded trial. J Perinat Med 2015;43:641.https://doi.org/10.1515/jpm-2015-0262.

    • PubMed
    • Export Citation
  • 24.

    Ogge, G, Chaiworapongsa, T, Romero, R, Hussein, Y, Kusanovic, JP, Yeo, L, et al. Placental lesions associated with maternal underperfusion are more frequent in early-onset than in late-onset preeclampsia. J Perinat Med 2011;39:641–52. https://doi.org/10.1515/jpm.2011.098.

    • PubMed
    • Export Citation
  • 25.

    Finkel, T, Deng, CX, Mostoslavsky, R. Recent progress in the biology and physiology of sirtuins. Nature 2009;460:587–91. https://doi.org/10.1038/nature08197.

    • Crossref
    • PubMed
    • Export Citation
  • 26.

    Arul Nambi Rajan, K, Khater, M, Soncin, F, Pizzo, D, Moretto-Zita, M, Pham, J, et al. Sirtuin1 is required for proper trophoblast differentiation and placental development in mice. Placenta 2018;62:1–8. https://doi.org/10.1016/j.placenta.2017.12.002.

    • Crossref
    • PubMed
    • Export Citation
  • 27.

    Pham, J, Arul Nambi Rajan, K, Li, P, Parast, MM. The role of Sirtuin1-PPAR gamma axis in placental development and function. J Mol Endocrinol 2018;60:R201–12. https://doi.org/10.1530/jme-17-0315.

    • Crossref
    • PubMed
    • Export Citation
  • 28.

    Poidatz, D, Dos Santos, E, Duval, F, Moindjie, H, Serazin, V, Vialard, F, et al. Involvement of estrogen-related receptor-gamma and mitochondrial content in intrauterine growth restriction and preeclampsia. Fertil Steril 2015;104:483–90.https://doi.org/10.1016/j.fertnstert.2015.05.005.

    • Crossref
    • PubMed
    • Export Citation
  • 29.

    Yin, Y, Feng, Y, Zhao, H, Zhao, Z, Yua, H, Xu, J, et al. SIRT1 inhibits releases of HMGB1 and HSP70 from human umbilical vein endothelial cells caused by IL-6 and the serum from a preeclampsia patient and protects the cells from death. Biomed Pharmacother 2017;88:449–58.https://doi.org/10.1016/j.biopha.2017.01.087.

    • Crossref
    • PubMed
    • Export Citation
  • 30.

    Wang, Y, Lewis, DF, Gu, Y, Zhao, S, Groome, LJ. Elevated maternal soluble Gp130 and IL-6 levels and reduced Gp130 and SOCS-3 expressions in women complicated with preeclampsia. Hypertension 2011;57:336–42.https://doi.org/10.1161/hypertensionaha.110.163360.

    • Crossref
    • PubMed
    • Export Citation
  • 31.

    Zhao, S, Gu, Y, Dong, Q, Fan, R, Wang, Y. Altered interleukin-6 receptor, IL-6R and gp130, production and expression and decreased SOCS-3 expression in placentas from women with pre-eclampsia. Placenta 2008;29:1024–8.https://doi.org/10.1016/j.placenta.2008.09.011.

    • Crossref
    • PubMed
    • Export Citation
  • 32.

    Wang, Y, Dong, Q, Gu, Y, Groome, LJ. Up-regulation of miR-203 expression induces endothelial inflammatory response: potential role in preeclampsia. Am J Reprod Immunol 2016;76:482–90.https://doi.org/10.1111/aji.12589.

    • Crossref
    • PubMed
    • Export Citation
  • 33.

    Jabalie, G, Ahmadi, M, Koushaeian, L, Eghbal-Fard, S, Mehdizadeh, A, Kamrani, A, et al. Metabolic syndrome mediates proinflammatory responses of inflammatory cells in preeclampsia. Am J Reprod Immunol 2019;81:e13086.https://doi.org/10.1111/aji.13086.

    • Crossref
    • PubMed
    • Export Citation
  • 34.

    Morbidelli, L, Chang, CH, Douglas, JG, Granger, HJ, Ledda, F, Ziche, M. Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium. Am J Physiol 1996;270:H411–5.https://doi.org/10.1152/ajpheart.1996.270.1.h411.

    • PubMed
    • Export Citation
  • 35.

    He, H, Venema, VJ, Gu, X, Venema, RC, Marrero, MB, Caldwell, RB. Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src. J Biol Chem1999; 274:25130–5.https://doi.org/10.1074/jbc.274.35.25130.

    • Crossref
    • PubMed
    • Export Citation
  • 36.

    Sha, Y, Zmijewski, J, Xu, Z, Abraham, E. HMGB1 develops enhanced proinflammatory activity by binding to cytokines. J Immunol 2008;180:2531–7.https://doi.org/10.4049/jimmunol.180.4.2531.

    • Crossref
    • PubMed
    • Export Citation
  • 37.

    Matias, ML, Romao, M, Weel, IC, Ribeiro, VR, Nunes, PR, Borges, VT, et al. Endogenous and uric acid-induced activation of NLRP3 inflammasome in pregnant women with preeclampsia. PLoS One 2015;10:e0129095.https://doi.org/10.1371/journal.pone.0129095.

    • Crossref
    • PubMed
    • Export Citation
  • 38.

    Ann-Charlotte, I. Inflammatory mechanisms in preeclampsia. Pregnancy Hypertens 2013;3:58.https://doi.org/10.1016/j.preghy.2013.04.005.

    • Crossref
    • PubMed
    • Export Citation
  • 39.

    Chen, Q, Yin, YX, Wei, J, Tong, M, Shen, F, Zhao, M, et al. Increased expression of high mobility group box 1 (HMGB1) in the cytoplasm of placental syncytiotrophoblast from preeclamptic placentae. Cytokine 2016;85:30–6.https://doi.org/10.1016/j.cyto.2016.06.001.

    • Crossref
    • PubMed
    • Export Citation
  • 40.

    Chao, J, Li, P, Chao, L. Kallistatin: double-edged role in angiogenesis, apoptosis and oxidative stress. Biol Chem 2017;398:1309–17.https://doi.org/10.1515/hsz-2017-0180.

    • Crossref
    • PubMed
    • Export Citation
  • 41.

    Chao, J, Stallone, JN, Liang, YM, Chen, LM, Wang, DZ, Chao, L. Kallistatin is a potent new vasodilator. J Clin Invest 1997;100:11–7.https://doi.org/10.1172/jci119502.

    • Crossref
    • PubMed
    • Export Citation
  • 42.

    Chen, LM, Ma, J, Liang, YM, Chao, L, Chao, J. Tissue kallikrein-binding protein reduces blood pressure in transgenic mice. J Biol Chem 1996;271:27590–4.https://doi.org/10.1074/jbc.271.44.27590.

    • Crossref
    • PubMed
    • Export Citation
  • 43.

    Chen, LM, Chao, L, Chao, J. Adenovirus-mediated delivery of human kallistatin gene reduces blood pressure of spontaneously hypertensive rats. Hum Gene Ther 1997;8:341–7.https://doi.org/10.1089/hum.1997.8.3-341.

    • Crossref
    • PubMed
    • Export Citation
  • 44.

    Shen, B, Smith, RSJr., Hsu, YT, Chao, L, Chao, J. Kruppel-like factor 4 is a novel mediator of Kallistatin in inhibiting endothelial inflammation via increased endothelial nitric-oxide synthase expression. J Biol Chem 2009;284:35471–8.https://doi.org/10.1074/jbc.m109.046813.

    • Crossref
    • PubMed
    • Export Citation
  • 45.

    Guo, Y, Li, P, Bledsoe, G, Yang, ZR, Chao, L, Chao, J. Kallistatin inhibits TGF-beta-induced endothelial-mesenchymal transition by differential regulation of microRNA-21 and eNOS expression. Exp Cell Res 2015;337:103–10.https://doi.org/10.1016/j.yexcr.2015.06.021.

    • Crossref
    • PubMed
    • Export Citation
  • 46.

    McMaster, WG, Kirabo, A, Madhur, MS, Harrison, DG. Inflammation, immunity, and hypertensive end-organ damage. Circ Res 2015;116:1022–33.https://doi.org/10.1161/circresaha.116.303697.

    • Crossref
    • PubMed
    • Export Citation
  • 47.

    Wang, CR, Chen, SY, Wu, CL, Liu, MF, Jin, YT, Chao, L, et al. Prophylactic adenovirus-mediated human kallistatin gene therapy suppresses rat arthritis by inhibiting angiogenesis and inflammation. Arthritis Rheum 2005;52:1319–24.https://doi.org/10.1002/art.20991.

    • Crossref
    • PubMed
    • Export Citation
  • 48.

    Chao, J, Yin, H, Yao, YY, Shen, B, Smith, RSJr., Chao, L. Novel role of kallistatin in protection against myocardial ischemia-reperfusion injury by preventing apoptosis and inflammation. Hum Gene Ther 2006;17:1201–13.https://doi.org/10.1089/hum.2006.17.1201.

    • Crossref
    • PubMed
    • Export Citation
  • 49.

    Li, P, Guo, Y, Bledsoe, G, Yang, ZR, Fan, H, Chao, L, et al. Kallistatin treatment attenuates lethality and organ injury in mouse models of established sepsis. Crit Care 2015;19:200.https://doi.org/10.1186/s13054-015-0919-4.

    • Crossref
    • PubMed
    • Export Citation
  • 50.

    Shen, B, Gao, L, Hsu, YT, Bledsoe, G, Hagiwara, M, Chao, L, et al. Kallistatin attenuates endothelial apoptosis through inhibition of oxidative stress and activation of Akt-eNOS signaling. Am J Physiol Heart Circ Physiol 2010;299:H1419–27.https://doi.org/10.1152/ajpheart.00591.2010.

    • Crossref
    • PubMed
    • Export Citation
  • 51.

    Liu, Y, Bledsoe, G, Hagiwara, M, Shen, B, Chao, L, Chao, J. Depletion of endogenous kallistatin exacerbates renal and cardiovascular oxidative stress, inflammation, and organ remodeling. Am J Physiol Ren Physiol 2012;303:F1230–8.https://doi.org/10.1152/ajprenal.00257.2012.

    • Crossref
    • Export Citation
  • 52.

    Chao, J, Guo, Y, Chao, L. Protective role of endogenous kallistatin in vascular injury and senescence by inhibiting oxidative stress and inflammation. Oxid Med Cell Longev 2018;2018:4138560.https://doi.org/10.1155/2018/4138560.

    • PubMed
    • Export Citation
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