Altered Level of Soluble fms-like Tyrosine Kinase 1 (sFlt1) and Hypoxia Inducible Factor-1alpha (HIF-1alpha) in Normotensive Pregnancy and Preeclampsia

John Wantania, Syakib Bakri, Karel Pandelaki, Maisuri Chalid

Abstract


BACKGROUND: Preeclampsia is still a significant problem worldwide. Of the many suggested mechanisms of its pathogenesis, the latest one is the balance of angiogenic factor and its relationship with hypoxia factors. The objective of this study was to observe changes or dynamic process of soluble fms-like tyrosine kinase 1 (sFlt1) as anti-angiogenic factor and hypoxia inducible factor 1-alpha (HIF-1α) as hypoxia marker in normotensive pregnancy and preeclampsia in mid-term and full-term pregnancies.

METHODS: A cohort study was conducted on 36 normotensive subjects, first examination was conducted at 20-28 weeks of gestation. Then second examination was conducted at the time of preeclampsia diagnosed or full-term pregnancy. Preeclampsia was characterized by hypertension of systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, with two readings separated in 4-6 hours period, and/or proteinuria with urine dipstick of ≥1+ or ≥300 mg per 24 hours. Examinations of sFlt-1 and HIF-1α were done by enzyme-linked immunosorbent assay method. Statistical analysis was done using a significance level of p<0.05.

RESULTS: Concentration of sFlt-1 was elevated in normotensive pregnancy and preeclampsia. Higher sFlt-1 concentration elevation was seen in preeclamptic group comparing to normotensive group, although not significant. This finding was related to the fact that investigated subjects were mostly developing mild preeclampsia merely. Comparing to normotensive group, preeclamptic group had higher HIF-1α concentration-per-week elevation, but not significant. There was a positive correlation between concentrations of sFlt-1 and HIF-1α, but not significant.

CONCLUSION: sFlt-1 concentration elevation was correlated with preeclampsia. Therefore comparing to averages, changes of sFlt-1 concentrations were more important. Concentrations of HIF-1α and sFlt-1 were positively correlated.

KEYWORDS: sFlt-1, HIF-1α, preeclampsia, normotension


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References


Osungbade KO, Ige OK. Public health perspectives of preeclampsia in developing countries: Implication for health system strengthening. J Pregnancy. 2011; 2011: 1-6, CrossRef.

Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: A systematic review. Lancet. 2006; 367: 1066-74, CrossRef.

Lyall F, Bellfort M. Pre-eclampsia: Etiology and Clinical Practice. New York: Cambridge University Press; 2007, NLMID.

Lam C, Lim KH, Karumanchi SA. Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia. Hypertension. 2005; 46: 1077-85, CrossRef.

Zagorska A, Dulak J. HIF-1: The known and unknown of hypoxia sensing. Acta Biochim Pol. 2004; 51: 563-78, PMID.

Conde-Agudelo A, Belizan JM. Risk factors for pre-eclampsia in a large cohort of Latin American and Caribbean women. Br J Obstet Gynecol. 2000; 107: 75-83, CrossRef.

Jasovic-Siveska E, Jasovic V, Stoilova S. Previous pregnancy history, parity, maternal age and risk of pregnancy induced hypertension. Bratisl Lek Listy. 2011; 112: 188-91, PMID.

Rudra CB, Williams MA, Schiff MA, Koenig JQ, Dills R, Yu J. A prospective study of maternal carboxyhemoglobin and preeclampsia risk. Paediatr Perinat Epidemiol. 2010; 24: 35-44, CrossRef.

Grill S, Rusterholz C, Zanetti-Dällenbach R, Tercanli S, Holzgreve W, Hahn S, et al. Potential markers of preeklamsi-a review. Reprod Biol Endocrinol. 2009; 7: 70, CrossRef.

Romero R, Nien JK, Espinoza J, Todem M, Fu W, Chung H, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med. 2008; 21: 9-23, CrossRef.

Park CW, Park JS, Shim SS, Jun JK, Yoon BH, Romero R. An elevated maternal plasma, but not amniotic fluid, soluble fms-like tyrosine kinase-1 (sFlt-1) at the time of mid-trimester genetic amniocentesis is a risk factor for preeclampsia. Am J Obstet Gynecol. 2005; 193: 984-9, CrossRef.

Chaiworapongsa T, Romero R, Espinoza, J, Bujold E, Kim Y M, Goncalves LF, et al. Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia. Am J Obstet Gynecol. 2004; 190: 1541-7, CrossRef.

Thomas CP, Andrews JI, Raikwar NS, Kelley EA, Herse F, Dechend R, et al. A recently evolved novel trophoblast-enriched secreted form of fms-like tyrosine kinase-1 variant is up-regulated in hypoxia and preeclampsia. J Clin Endocrinol Metab. 2009; 94: 2524-30, CrossRef.

Unal ER, Robinson CJ, Johnson DD, Chang EY. Second-trimester angiogenic factors as biomarkers for future-onset preeclampsia. Am J Obstet Gynecol. 2007; 197: 211.e1-4, CrossRef.

Perni U, Sison C, Sharma V, Helseth G, Hawfield A, Suthanthiran M, et al. Angiogenic factors in superimposed preeclampsia: a longitudinal study of women with chronic hypertension during pregnancy. Hypertens. 2012; 59: 740-6, CrossRef.

Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004; 350: 672-83, CrossRef.

Haggerty CL, Seifert ME, Tang G, Olsen J, Bass DC, Karumanchi SA, et al. Second trimester anti-angiogenic proteins and preeclampsia. Pregnancy Hypertens. 2012; 2: 158-63, CrossRef.

Peng M, Ding Y, Yu L, Zhou C. Change of HIF-1α protein expression in the placenta bed and concentration of vWF in maternal peripheral blood of pre-eclampsia. J Central South Univ. 2010; 35: 134-9, PMID.

Soleymanlou N, Jurisica I, Nevo O, Ietta F, Zhang X, Zamudio S, et al. Molecular evidence of placental hypoxia in preeclampsia. J Clin Endocrinol Metab. 2005; 90: 4299-308, CrossRef.

Tal R, Shaish A, Barshack I, Polak-Charcon S, Afek A, Volkov A, et al. Effects of hypoxia-inducible factor-1alpha overexpression in pregnant mice: possible implications for preeclampsia and intrauterine growth restriction. Am J Pathol. 2010; 177: 2950-62, CrossRef.

Akhilesh M, Mahalingam V, Nalliah S, Ali RM, Ganesalingam M, Haleagrahara N. Hypoxia-inducible factor-1a as a predictive marker in pre-eclampsia. Biomed Reports. 2013; 1: 257-8, CrossRef.




DOI: https://doi.org/10.18585/inabj.v5i2.61

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