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Talk about the darling of the preeclampsia screening field-placental growth factor (3) | PLGF and receptor sFlt-1

Talk about the darling of the preeclampsia screening field-placental growth factor (3) | PLGF and receptor sFlt-1

(Summary description)

Talk about the darling of the preeclampsia screening field-placental growth factor (3) | PLGF and receptor sFlt-1

(Summary description)

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Studies have shown that in pregnant women with preeclampsia, the concentration of sFlt-1 increases and the concentration of PLGF decreases [1]. The changes in the concentration levels of the two indicate the development of subsequent illnesses in pregnant women with suspected preeclampsia.

In this issue, let’s talk about PLGF and the receptor sFlt-1.

 

#1

What is sFlt-1?

 

Soluble fms-like tyrosine kinase 1 (sFlt-1) is a circulating anti-angiogenic protein. sFlt-1 is spliced from the extracellular domain of Flt-1 (VEGFR-1) (vascular endothelial growth factor receptor 1), transcribed at intron 13, and only encodes the extracellular domain, which is the entry of VEGFR-1 into the maternal blood The soluble form of circulation [2]. sFlt-1 is secretable and retains a high affinity for PLGF [3].

In 1996, Kendall et al. [4] first discovered free Flt-1 (sFlt-1) in the culture medium of human umbilical vein endothelial cells, and found that sFlt-1 has a strong affinity with vascular endothelial growth factor (VEGF). Able to form a stable complex.

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In 1998, Clark et al. [5] used the slices of human placental tissues during early pregnancy and full-term, and through in situ hybridization, Western Blot and immunohistochemistry tests, for the first time in human placental tissues (extravillous trophoblast cells and trophoblast cells). SFlt-1 is found in the villi.

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#2

What is the relationship between PLGF and sFlt-1?

 

sFlt-1 works by attaching to the receptor binding domains of placental growth factor (PLGF) and vascular endothelial growth factor (VEGF), preventing their interaction with endothelial receptors, thereby inducing endothelial dysfunction [1]. PLGF has a high degree of homology with VEGF. PLGF plays a role in enhancing the proliferation and implantation of trophoblasts, and sFlt-1 competes with VEGFR-1 to inhibit the activity of PLGF [3].

 

#3

PLGF、sFlt-1与子痫前期?

 

滋养细胞侵袭不足,子宫螺旋动脉血管重铸障碍,导致胎盘血流灌注不足,是子痫前期发病的关键。螺旋动脉重建损伤,胎盘灌注减少,导致胎盘缺血和sFlt-1释放。sFlt-1与游离的PLGF和VEGF相结合,从而导致内皮功能障碍。内皮细胞的生理功能障碍触发了内皮素-1(ET-1)的产生,从而进一步诱导高血压和蛋白尿,并抑制肾素的释放,促使高血压和PE的发生[2]

 

Levine等[1]开展了一项随机、双盲的临床试验。4598名孕妇招募入组。实验组:120例子痫前期孕妇;对照组:120例正常孕妇。在连续几个不同的孕周,均测定sFlt-1,PLGF。

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Research indicates:

1) The sFlt-1 of pregnant women with PE in the later period is significantly higher than that of normal pregnant women;

2) sFlt-1 increased significantly within 5 weeks before the occurrence of PE;

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3)Pregnant women with PE in the later period have significantly lower PLGF than normal pregnant women since 13-16 weeks;

4) PLGF reduction is 9-11 weeks earlier than hypertension proteinuria.

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The special concentration level changes of PLGF and sFlt-1 in the mother’s body have predictive value for the occurrence of preeclampsia in pregnant women with suspected preeclampsia in the second and third trimesters (the expression level of sFlt-1 has no change before 20 weeks of pregnancy. Pre-predictions are meaningless).

 

#4

Comparison of the value of PLGF and sFlt-1 in predicting preeclampsia

 

Medical value comparison

 

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In summary,

1)First trimesterUse of combined maternal risk factors, MAP, PLGF, UTPIPreeclampsia risk prediction model predicts PE best;

2)In the second and third trimester, PLGF detection and sFlt-1/PLGFThe short-term PE risk prediction is of equal value.Research has shown that,PLGF repeated dynamic monitoring has high accuracy and sensitivity in predicting preterm birth, and may improve the level of risk management.

 

Economic value comparison

 

1、The use of preeclampsia risk prediction models in the first trimester can save national medical expenses

 

A study conducted in Canada showed that high-risk pregnant women who were screened for preeclampsia in the first trimester took a small dose of aspirin for prophylaxis, and it is estimated that about 14 million Canadian dollars can be saved each year [6].

Canada delivered about 387,000 a year (2015), while China delivered about 15.23 million a year (2018), about 40 times that of Canada.Carrying out the early pregnancy risk assessment project saves about 2.8 billion medical economic expenditures every year.

 

2、Comparison of health economics using PLGF test or sFlt-1/PLGF ratio test in the second and third trimester

 

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Whether it is PLGF detection or sFlt-1/PLGF ratio detection, compared with conventional detection,Treatment costs are all saved.PLGF detection ratio sFlt-1/PLGF ratio detection it can save up to 2.1 times the cost of diagnosis and treatment.

 

Summary

1) Soluble fms-like tyrosine kinase 1 (sFlt-1) is a circulating anti-angiogenic protein;

2) In pregnant women with preeclampsia, the concentration of sFlt-1 increases and the concentration of PLGF decreases. The special concentration level changes of PLGF and sFlt-1 in the mother's body have predictive value for the occurrence of PE in pregnant women with suspected preeclampsia;

3) Pre-eclampsia risk prediction model combined with maternal risk factors, MAP, PLGF, UTPI in early pregnancy predicts PE best;

4) In the second and third trimesters, PLGF detection and sFlt-1/PLGF have the same predictive value, and repeated dynamic detection of PLGF has high accuracy and sensitivity for predicting preterm birth, which may improve the level of risk management;

5) Reasonable and effective management of preeclampsia can save medical expenses. The use of the preeclampsia risk assessment model in the first trimester is expected to save about 2.8 billion medical expenditures in my country each year. The PLGF detection in the middle and late pregnancy can save up to 2.1 times the diagnosis and treatment costs compared to the sFlt-1/PLGF ratio detection.

 

In the next issue, we will talk about how PLGF promotes angiogenesis.

 

References:

[1] Levine RJ, et al. Circulating Angiogenic Factors and the Risk of Preeclampsia[J]. New England Journal of Medicine, 2004, 350(7):672.

[2] Jena MK, et al. Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta[J]. Biomolecules, 2020, 10(6).

[3] Shen Jing. The diagnostic and predictive value of sFlt-1, PlGF, and sFlt-/PlGF in hypertension during pregnancy[D]. Chinese Academy of Medical Sciences, 2012.

[4] Kendall RL, et al. Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR.[J]. Biochem Biophys Res Commun, 1996, 226(2):324-328.

[5] Clark DE, et al. A Vascular Endothelial Growth Factor Antagonist Is Produced by the Human Placenta and Released into the Maternal Circulation[J]. Biology of Reproduction, 1998, 59(6):1540-8.

[6] Poon LC, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre‐eclampsia: A pragmatic guide for first‐trimester screening and prevention[J]. International Journal of Gynecology & Obstetrics. 2019; 145:1-27.

[7] Kate ED, et al. Placental growth factor testing to access women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedage cluster- randomised controlled trial[J]. Lancet. 2019; 6736(18): 33212-4.

[8] Zeisler H, et al. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia.[J]. N Engl J Med, 2016, 374(1):13-22.

[9] Duhig KE, et al. Diagnostic accuracy of repeat placental growth factor measurements in women with suspected preeclampsia: A case series study[J]. Acta Obstetricia et Gynecologica Scandinavica. 2020; 00:1-9.

[10] The Triage PlGF test, Elecsys immunoassay sFlt-1/PlGF ratio, DELFIA Xpress PlGF 1-2-3 test and BRAHMS sFlt-1 Kryptor / PlGF plus Kryptor PE ratio to aid the assessment of suspected pre-eclampsia | Guidance and guidelines | NICE[J]. 2016: 1-47.

 

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