Effective prediction of preeclampsia by measuring serum angiotensin II, urinary angiotensinogen and urinary transforming growth factor β1

Zhang,Lihong; Zhou,Yunjiao; Wu,Qing; Fan,Weifeng; Ye,Jun; Chen,Yaping; Wu,Yun; Niu,Jianying; Gu,Yong

doi:10.3892/etm.2017.4484

Effective prediction of preeclampsia by measuring serum angiotensin II, urinary angiotensinogen and urinary transforming growth factor β1

Authors:
- Lihong Zhang
- Yunjiao Zhou
- Qing Wu
- Weifeng Fan
- Jun Ye
- Yaping Chen
- Yun Wu
- Jianying Niu
- Yong Gu
View Affiliations

Affiliations: Department of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, P.R. China
Published online on: May 22, 2017 https://doi.org/10.3892/etm.2017.4484
Pages: 391-397
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the current study was to analyze serum angiotensin II (Ang II), urinary angiotensinogen (AGT) and urinary transforming growth factor β1 (TGFβ1) levels in relation to the clinical manifestation of preeclampsia, and to explore the effects of circulating and renal renin angiotensin system (RAS) in preeclampsia patients. An enzyme-linked immunosorbent assay was used to evaluate serum Ang II, urinary AGT and urinary TGFβ1 in preeclampsia, pregnancy‑induced hypertension and normotensive pregnancy patients. The correlation between urinary AGT and serum Ang II, urinary TGFβ1, blood pressure and urinary albumin/creatinine ratio (ACR) were then analyzed. Receiver operating characteristic (ROC) curves were also constructed. Negative correlations were observed between urinary AGT and blood pressure, and urinary AGT and ACR, whereas positive correlations were found between urinary AGT and serum Ang II, and urinary AFT and TGFβ1. Moreover, the area under the curve (AUC) of AGT was 0.841 [95% confidence interval (CI): 0.742‑0.940, P<0.001], which was significantly higher than that of serum Ang II or urinary TGFβ1 (P<0.001). The optimal cut‑off value of urinary AGT at 193 ng/l showed a high diagnostic value in preeclampsia. The AUC of combined serum Ang II, urinary AGT and urinary TGFβ1 was 0.918 (95% CI: 0.845‑0.990, P<0.001), with a sensitivity of 83.9% and a specificity of 89.7%. Decreased levels of urinary AGT in preeclampsia patients suggested that local renal RAS was suppressed, and this was associated with hypertension and proteinuria. A high value preeclampsia diagnosis could be achieved by measuring urinary AGT or a combination of urinary AGT, serum Ang II and urinary TGFβ1.

View Figures

View References

1	Redman CW and Sargent IL: Latest advances in understanding preeclampsia. Science. 308:1592–1594. 2005. View Article : Google Scholar : PubMed/NCBI
2	Sibai B, Dekker G and Kupferminc M: Pre-eclampsia. Lancet. 365:785–799. 2005. View Article : Google Scholar : PubMed/NCBI
3	Noris M, Perico N and Remuzzi G: Mechanisms of disease: Pre-eclampsia. Nat Clin Pract Nephrol. 1:98–114; quiz 120. 2005. View Article : Google Scholar : PubMed/NCBI
4	Irani RA and Xia Y: The functional role of the renin-angiotensin system in pregnancy and preeclampsia. Placenta. 29:763–771. 2008. View Article : Google Scholar : PubMed/NCBI
5	Chung O, Kuhl H, Stoll M and Unger T: Physiological and pharmacological implications of AT1 versus AT2 receptors. Kidney Int Suppl. 67:S95–S99. 1998. View Article : Google Scholar : PubMed/NCBI
6	Langer B, Grima M, Coquard C, Bader AM, Schlaeder G and Imbs JL: Plasma active renin, angiotensin I, and angiotensin II during pregnancy and in preeclampsia. Obstet Gynecol. 91:196–202. 1998. View Article : Google Scholar : PubMed/NCBI
7	Brown MA, Zammit VC, Mitar DA and Whitworth JA: Renin-aldosterone relationships in pregnancy-induced hypertension. Am J Hypertens. 5:366–371. 1992. View Article : Google Scholar : PubMed/NCBI
8	Sanchez-Aranguren LC, Prada CE, Riano-Medina CE and Lopez M: Endothelial dysfunction and preeclampsia: Role of oxidative stress. Front Physiol. 5:3722014. View Article : Google Scholar : PubMed/NCBI
9	Roberts AB and Sporn MB: Transforming growth factor-beta: Potential common mechanisms mediating its effects on embryogenesis, inflammation-repair, and carcinogenesis. Int J Rad Appl Instrum B. 14:435–439. 1987. View Article : Google Scholar : PubMed/NCBI
10	Akhurst RJ, FitzPatrick DR, Gatherer D, Lehnert SA and Millan FA: Transforming growth factor betas in mammalian embryogenesis. Prog Growth Factor Res. 2:153–168. 1990. View Article : Google Scholar : PubMed/NCBI
11	Bertolino P, Deckers M, Lebrin F and ten Dijke P: Transforming growth factor-beta signal transduction in angiogenesis and vascular disorders. Chest. 128 6 Suppl:585S–590S. 2005. View Article : Google Scholar : PubMed/NCBI
12	Lebrin F, Deckers M, Bertolino P and Ten Dijke P: TGF-beta receptor function in the endothelium. Cardiovasc Res. 65:599–608. 2005. View Article : Google Scholar : PubMed/NCBI
13	Ferrari G, Pintucci G, Seghezzi G, Hyman K, Galloway AC and Mignatti P: VEGF, a prosurvival factor, acts in concert with TGF-beta1 to induce endothelial cell apoptosis. Proc Natl Acad Sci USA. 103:pp. 17260–17265. 2006; View Article : Google Scholar : PubMed/NCBI
14	Sales VL, Engelmayr GC Jr, Mettler BA, Johnson JA Jr, Sacks MS and Mayer JE Jr: Transforming growth factor-beta1 modulates extracellular matrix production, proliferation, and apoptosis of endothelial progenitor cells in tissue-engineering scaffolds. Circulation. 114 1 Suppl:I193–I199. 2006. View Article : Google Scholar : PubMed/NCBI
15	Bommireddy R and Doetschman T: TGFbeta1 and Treg cells: Alliance for tolerance. Trends Mol Med. 13:492–501. 2007. View Article : Google Scholar : PubMed/NCBI
16	Karmakar S and Das C: Regulation of trophoblast invasion by IL-1beta and TGF-beta1. Am J Reprod Immunol. 48:210–219. 2002. View Article : Google Scholar : PubMed/NCBI
17	Power LL, Popplewell EJ, Holloway JA, Diaper ND, Warner JO and Jones CA: Immunoregulatory molecules during pregnancy and at birth. J Reprod Immunol. 56:19–28. 2002. View Article : Google Scholar : PubMed/NCBI
18	Zhao MR, Qiu W, Li YX, Zhang ZB, Li D and Wang YL: Dual effect of transforming growth factor beta1 on cell adhesion and invasion in human placenta trophoblast cells. Reproduction. 132:333–341. 2006. View Article : Google Scholar : PubMed/NCBI
19	Ayatollahi M, Geramizadeh B, Yazdani M and Azarpira N: Effect of the immunoregulatory cytokines on successful pregnancy depends upon the control of graft rejection mechanisms. Transplant Proc. 39:pp. 244–245. 2007; View Article : Google Scholar : PubMed/NCBI
20	Murakami K, Takemura T, Hino S and Yoshioka K: Urinary transforming growth factor-beta in patients with glomerular diseases. Pediatr Nephrol. 11:334–336. 1997. View Article : Google Scholar : PubMed/NCBI
21	Powe CE, Levine RJ and Karumanchi SA: Preeclampsia, a disease of the maternal endothelium: The role of antiangiogenic factors and implications for later cardiovascular disease. Circulation. 123:2856–2869. 2011. View Article : Google Scholar : PubMed/NCBI
22	Senatorski G, Paczek L, Sułowicz W, Gradowska L and Bartłomiejczyk I: Urine activity of cathepsin B, collagenase and urine excretion of TGF-beta 1 and fibronectin in membranous glomerulonephritis. Res Exp Med (Berl). 198:199–206. 1998. View Article : Google Scholar : PubMed/NCBI
23	Blush J, Lei J, Ju W, Silbiger S, Pullman J and Neugarten J: Estradiol reverses renal injury in Alb/TGF-beta1 transgenic mice. Kidney Int. 66:2148–2154. 2004. View Article : Google Scholar : PubMed/NCBI
24	Potier M, Elliot SJ, Tack I, Lenz O, Striker GE, Striker LJ and Karl M: Expression and regulation of estrogen receptors in mesangial cells: Influence on matrix metalloproteinase-9. J Am Soc Nephrol. 12:241–251. 2001.PubMed/NCBI
25	Hodari AA, Smeby R and Bumpus FM: A renin-like substance in the human placenta. Obstet Gynecol. 29:313–317. 1967.PubMed/NCBI
26	Symonds EM, Stanley MA and Skinner SL: Production of renin by in vitro cultures of human chorion and uterine muscle. Nature. 217:1152–1153. 1968. View Article : Google Scholar : PubMed/NCBI
27	Cheung KL and Lafayette RA: Renal physiology of pregnancy. Adv Chronic Kidney Dis. 20:209–214. 2013. View Article : Google Scholar : PubMed/NCBI
28	Barreras A and Gurk-Turner C: Angiotensin II receptor blockers. Proc (Bayl Univ Med Cent). 16:pp. 123–126. 2003; PubMed/NCBI
29	Gilbert JS, Ryan MJ, LaMarca BB, Sedeek M, Murphy SR and Granger JP: Pathophysiology of hypertension during preeclampsia: Linking placental ischemia with endothelial dysfunction. Am J Physiol Heart Circ Physiol. 294:H541–H550. 2008. View Article : Google Scholar : PubMed/NCBI
30	Alexander BT, Cockrell K, Cline FD, Llinas MT, Sedeek M and Granger JP: Effect of angiotensin II synthesis blockade on the hypertensive response to chronic reductions in uterine perfusion pressure in pregnant rats. Hypertension. 38:742–745. 2001. View Article : Google Scholar : PubMed/NCBI
31	Kobori H, Nishiyama A, Harrison-Bernard LM and Navar LG: Urinary angiotensinogen as an indicator of intrarenal Angiotensin status in hypertension. Hypertension. 41:42–49. 2003. View Article : Google Scholar : PubMed/NCBI
32	Wiesel P, Mazzolai L, Nussberger J and Pedrazzini T: Two-kidney, one clip and one-kidney, one clip hypertension in mice. Hypertension. 29:1025–1030. 1997. View Article : Google Scholar : PubMed/NCBI