Could AGEs be markers of pre-eclampsia? Study of concentration of advanced protein glycation products in pregnant women with physiological pregnancy and pregnancy complicated with pre-eclampsia

• Authors: Piotr Bodzek , Iwona Janosz , Aleksandra Damasiewicz-Bodzek , Łukasz Witek , Anita Olejek

Title variants

PL

Czy AGEs mogą być markerami stanu przedrzucawkowego? Badanie stężenia zaawansowanych produktów glikacji białek u kobiet ciężarnych z ciążą fizjologiczną i ciążą powikłaną stanem przedrzucawkowym

• Languages of publication: EN PL

Abstracts

EN

INTRODUCTION: The role of advanced glycation end products (AGEs) in the pathomechanism of arterial hypertension has been demonstrated, but little information is available on the influence of AGEs on the course of pre-eclampsia (PE). The aim of the study was to assess the concentration profile of advanced protein glycation products in pregnant women diagnosed with PE. MATERIAL AND METHODS: The concentrations of AGEs, carboxymethyllysine (CML), carboxyethyllysine (CEL) and methylglyoxal (MG) in the sera of female respondents were determined using the enzyme immunoassay method. RESULTS: The levels of AGE and CML were lower in the group of women with PE compared to the group of non- -pregnant women (p = 0.0411 and p = 0.0072). A lower CML concentration was found in healthy pregnant women as compared to healthy non-pregnant women (p = 0.00068). Positive correlations were found between AGE and CML levels in women with PE (R = 0.339, p = 0.032) and between CML and CEL in healthy non-pregnant women (R = 0.447, p = 0.012). CONCLUSIONS:We suggest that there is a decrease in the intensity of non-enzymatic protein glycation during pregnancy. Moreover, our study indicates that isolated PE may be associated with a different pathomechanism than chronic hypertension, and therefore AGEs cannot be at present considered a marker of PE.

PL

WSTĘP: Rola końcowych produktów zaawansowanejglikacji (advanced glycation end products – AGEs) w patomechanizmie nadciśnienia tętniczego została udowodniona, jednak niewiele jest informacji na temat wpływu AGEs na przebieg stanu przedrzucawkowego (pre-eclampsia – PE). Celem pracy była ocena profilu stężeń zaawansowanych pro-duktów glikacji białek u kobiet ciężarnych z rozpoznaniem PE. MATERIAŁ I METODY: Oznaczenia stężeń AGEs, karboksymetylolizyny (carboxymethyllysine – CML), karboksyetylolizyny (carboxyethyllysine – CEL) i metyloglioksalu (methylglyoxal – MG) w surowicy badanych kobiet wykonano metodą immunoenzymatyczną. WYNIKI: Stężenia AGE i CML były niższe w grupie kobiet z PE w porównaniu z grupą kobiet nieciężarnych (p = 0,0411 i p = 0,0072). Stwierdzono niższe stężenie CML u zdrowych ciężarnych w porównaniu ze zdrowymi nieciężarnymi (p = 0,00068). Stwierdzono dodatnie korelacje pomiędzy stężeniem AGE i CML u kobiet z PE (R = 0,339, p = 0,032) oraz pomiędzy CML i CEL u zdrowych kobiet nieciężarnych (R = 0,447, p = 0,012). WNIOSKI: Sugerujemy, że w czasie ciąży dochodzi do zmniejszenia intensywności nieenzymatycznej glikacji białek. Ponadto nasze badanie wskazuje, że izolowane PE może być związane z innym patomechanizmem niż przewlekłe nadciśnienie tętnicze i dlatego AGEs nie mogą być obecnie uważane za marker PE.

Keywords

EN

AGEs; advanced glycation end products; ciąża; nieenzymatyczna glikozylacja; non-enzymatic glycosylation; pre-eclampsia; pregnancy; stan przedrzucawkowy; zaawansowane produkty glikacji białek

Discipline

• MEDICINE: MEDICINE

• Publisher: Śląski Uniwersytet Medyczny w Katowicach
• Journal: Annales Academiae Medicae Silesiensis
• Year: 2022
• Issue: 76
• Pages: 106-111

Contributors

author

Piotr Bodzek

• Department of Gynaecology, Obstetrics and Oncological Gynaecology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland

author

Iwona Janosz

• Department of Gynaecology, Obstetrics and Oncological Gynaecology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland

author

Aleksandra Damasiewicz-Bodzek

• Department of Chemistry, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland

author

Łukasz Witek

• Department of Gynaecology, Obstetrics and Oncological Gynaecology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland

author

Anita Olejek

• Department of Gynaecology, Obstetrics and Oncological Gynaecology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland

References

• 1. Shen C.Y., Lu C.H., Wu C.H., Li K.J., Kuo Y.M., Hsieh S.C. et al. The development of Maillard reaction, and advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling inhibitors as novel therapeutic strategies for patients with AGE-related diseases. Molecules 2020; 25(23): 5591, doi: 10.3390/molecules25235591.
• 2. Perrone A., Giovino A., Benny J., Martinelli F. Advanced glycation end products (AGEs): biochemistry, signaling, analytical methods, and epigenetic effects. Oxid. Med. Cell. Longev. 2020; 2020: 3818196, doi: 10.1155/2020/3818196.
• 3. Emidio G.D., Placidi M., Rea F., Rossi G., Falone S., Cristiano L. et al. Methylglyoxal-dependent glycative stress and deregulation of SIRT1 functional network in the ovary of PCOS mice. Cells 2020; 9(1): 209, doi: 10.3390/cells9010209.
• 4. Leerach N., Harashima A., Munesue S., Kimura K., Oshima Y., Goto H. et al. Glycation reaction and the role of the receptor for advanced glycation end-products in immunity and social behavior. Glycoconj. J. 2021; 38(3): 303–310, doi: 10.1007/s10719-020-09956-6.
• 5. Stowell S.R., Ju T., Cummings R.D. Protein glycosylation in cancer. Annu. Rev. Pathol. 2015; 10: 473–510, doi: 10.1146/annurev-pathol-012414-040438.
• 6. Pertyńska-Marczewska M., Głowacka E., Sobczak M., Cypryk K., Wil-czyński J. Glycation endproducts, soluble receptor for advanced glycation endproducts and cytokines in diabetic and non-diabetic pregnancies. Am. J. Reprod. Immunol. 2009; 61(2): 175–182, doi: 10.1111/j.1600-0897.2008.00679.x.
• 7. Alexander K.L., Mejia C.A., Jordan C., NelsonM.B., Howell B.M., Jones C.M. et al. Differential receptor for advanced glycation end products expression in preeclamptic, intrauterine growth restricted, and gestational diabetic placentas. Am. J. Reprod. Immunol. 2016; 75(2): 172–180, doi: 10.1111/aji.12462.
• 8. Prasad K., Mishra M. Do advanced glycation end products and its receptor play a role in pathophysiology of hypertension? Int. J. Angiol. 2017; 26(1): 1–11, doi: 10.1055/s-0037-1598183.
• 9. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet. Gynecol. 2013; 122(5): 1122–1131, doi: 10.1097/01.AOG.0000437382.03963.88.
• 10. Akasaka J., Naruse K., Sado T., Uchiyama T., Makino M., Yamauchi A. et al. Involvement of receptor for advanced glycation endproducts in hypertensive disorders of pregnancy. Int. J. Mol. Sci. 2019; 20(21): 5462, doi: 10.3390/ijms20215462.
• 11. Pierik E., Prins J.R., van Goor H., Dekker G.A., Daha M.R., Seelen M.A.J. et al. Dysregulation of complement activation and placental dysfunction: a potential target to treat preeclampsia? Front. Immunol. 2020; 10: 3098, doi: 10.3389/fimmu.2019.03098.
• 12. Valencia-Ortega J., Zárate A., Saucedo R., Hernández-Valencia M., Cruz J.G., Puello E. Placental proinflammatory state and maternal endothelial dysfunction in preeclampsia. Gynecol. Obstet. Invest. 2019; 84(1): 12–19, doi: 10.1159/000491087.
• 13. Feng C., Tao Y., Shang T., Yu M. Calprotectin, RAGE and TNF-α in hypertensive disorders in pregnancy: expression and significance. Arch. Gynecol. Obstet. 2011; 283(2): 161–166, doi: 10.1007/s00404-009-1303-x.
• 14. Azizian-Farsani F., Abedpoor N., Hasan Sheikhha M., Gure A.O., Nasr-Esfahani M.H., Ghaedi K. Receptor for advanced glycation end products acts as a fuel to colorectal cancer development. Front. Oncol. 2020; 10: 552283, doi: 10.3389/fonc.2020.552283.
• 15. Gyselaers W. Preeclampsia is a syndrome with a cascade of pathophysiologic events. J. Clin. Med. 2020; 9(7): 2245, doi: 10.3390/jcm9072245.
• 16. Šebeková K., Gurecká R., Csongová M., Koborová I., Šebek J. Sex differences in association of elevated blood pressure with variables characterizing cardiometabolic risk in young subjects with or without metabolic abnormalities. Int. J. Environ. Res. Public Health 2020; 17(10): 3612, doi: 10.3390/ijerph17103612.
• 17. García-Gómez E., Bobadilla-Bravo M., Díaz-Díaz E., Vázquez-Martínez E.R., Nava-Salazar S., Torres-Ramos Y. et al. High plasmatic levels of advanced glycation end products are associated with metabolic alterations and insulin resistance in preeclamptic women. Curr. Mol. Med. 2020; 20(9): 751–759, doi: 10.2174/1566524020666200220141414.
• 18. Chen W., Zhang Y., Yue C., Ye Y., Chen P., Peng W. et al. Accumulation of advanced glycation end products involved in inflammation and contributing to severe preeclampsia, in maternal blood, umbilical blood and placental tissues. Gynecol. Obstet. Invest. 2017; 82(4): 388–397, doi: 10.1159/000448141.
• 19. Kansu-Celik H., Tasci Y., Karakaya B.K., Cinar M., Candar T., Caglar G.S. Maternal serum advanced glycation end products level as an early marker for predicting preterm labor/PPROM: a prospective preliminary study. J. Matern. Fetal Neonatal Med. 2019; 32(16): 2758–2762, doi: 10.1080/14767058.2018.1449202.
• 20. Carnevale D., Mascio G., D'Andrea I., Fardella V., Bell R.D., Branchi I. et al. Hypertension induces brain β-amyloid accumulation, cognitive impairment, and memory deterioration through activation of receptor for advanced glycation end products in brain vasculature. Hypertension 2012; 60(1): 188–197, doi: 10.1161/HYPERTENSIONAHA.112.195511.
• 21. de Ranitz-Greven W.L., Kaasenbrood L., Poucki W.K., Hamerling J., Bos D.C., Visser G.H. et al. Advanced glycation end products, measured as skin autofluorescence, during normal pregnancy and pregnancy complicated by diabetes mellitus. Diabetes Technol. Ther. 2012; 14(12): 1134–1139, doi: 10.1089/dia.2012.0120.
• 22. Fasshauer M., Seeger J., Waldeyer T., Schrey S., Ebert T., Lossner U. et al. Endogenous soluble receptor for advanced glycation endproducts is increased in preeclampsia. J. Hypertens. 2008; 26(9): 1824–1828, doi: 10.1097/HJH.0b013e3283060c5c.
• 23. Kold-Christensen R., Johannsen M. Methylglyoxal metabolism and aging-related disease: moving from correlation toward causation. Trends Endocrinol. Metab. 2020; 31(2): 81–92, doi: 10.1016/j.tem.2019.10.003.
• 24. Sankaralingam S., Xu H., Jiang Y., Sawamura T., Davidge S.T. Evidence for increased methylglyoxal in the vasculature of women with preeclampsia: role in upregulation of LOX-1 and arginase. Hypertension 2009; 54(4): 897–904, doi: 10.1161/HYPERTENSIONAHA.109.135228.
• 25. Dhar I., Dhar A., Wu L., Desai K.M. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats. PLoS One 2013; 8(9): e74212, doi: 10.1371/journal.pone.0074212.
• 26. Piuri G., Basello K., Rossi G., Soldavini C.M., Duiella S., Privitera G. et al. Methylglyoxal, glycated albumin, PAF, and TNF-alpha: possible inflammatory and metabolic biomarkers for management of gestational diabetes. Nutrients 2020; 12(2): 479, doi: 10.3390/nu12020479.
• 27. Hanssen N.M.J., Scheijen J.L.J.M., Jorsal A., Parving H.H., Tarnow L., Rossing P. et al. Higher plasma methylglyoxal levels are associated with incident cardiovascular disease in individuals with type 1 diabetes: a 12-year follow-up study. Diabetes 2017; 66(8): 2278–2283, doi: 10.2337/db16-1578.
• 28. Janšáková K., Lengyelová E., Pribulová N., Somoza V., Celec P., Šebeková K. et al. Metabolic and renal effects of dietary advanced glycation end products in pregnant rats – a pilot study. Physiol. Res. 2019; 68(3): 467– –479, doi: 10.33549/physiolres.934102.
• 29. Luevano-Contreras C., Chapman-Novakofski K. Dietary advanced glycation end products and aging. Nutrients 2010; 2(12): 1247–1265, doi: 10.3390/nu2121247.
• 30. Oliver E.A., Buhimschi C.S., Dulay A.T., BaumbuschM.A., Abdel-Razeq S.S., Lee S.Y. et al. Activation of the receptor for advanced glycation end products system in women with severe preeclampsia. J. Clin. Endocrinol. Metab. 2011; 96(3): 689–698, doi: 10.1210/jc.2010-1418.
• 31. Gradmark A., Pomeroy J., Renström F., Steiginga S., Persson M., Wright A. et al. Physical activity, sedentary behaviors, and estimated insulin sensitivity and secretion in pregnant and non-pregnant women. BMC Pregnancy Childbirth 2011; 11: 44, doi: 10.1186/1471-2393-11-44.
• 32. Teissier T., Boulanger É. The receptor for advanced glycation end- -products (RAGE) is an important pattern recognition receptor (PRR) for inflammaging. Biogerontology 2019; 20(3): 279–301, doi: 10.1007/s10522-019-09808-3.
• 33. Hernandez T.L., Friedman J.E., Van Pelt R.E., Barbour L.A. Patterns of glycemia in normal pregnancy: should the current therapeutic targets be challenged? Diabetes Care 2011; 34(7): 1660–1668, doi: 10.2337/dc11-0241.

• Document Type: article