The role of a novel angiogenesis related protein, FKBPL, in spiral uterine artery remodelling important for the pathogenesis of preeclampsia

Ross McNally, Naomi Todd, Abdelrahim Alqudah, Tracy Robson, David Grieve, Lana McClements

Research output: Contribution to conferenceAbstract

Abstract

Introduction Preeclampsia is a complication which occurs in 5%–6% of pregnancies, characterised by high blood pressure and/or other organ dysfunction in the third trimester of pregnancy. Preeclampsia has short-term risks for the mother and child, but is also associated with remote cardiovascular disease and/or type 2 diabetes mellitus in both. The pathogenesis of preeclampsia is unclear but it appears to be attributed to inappropriate remodelling of spiral uterine artery as a result of dysregulated trophoblast function. We investigated the involvement of novel regulator of developmental and pathological angiogenesis, FKBPL, and its role in the pathophysiology of preeclampsia. Methods Trophoblast cells (HTR8.SV.neo, BeWo and JAR) were exposed to hypoxic (1%) or normoxic (21%) conditions before wound scratch migration assays were performed, and FKBPL protein levels measured. BeWo cells were treated with the HIF-1α activator, DMOG, for 24 hour before protein lysates were extracted for western blotting analysis. Colony forming efficiency and the number of holoclones, meroclones and paraclones of both HTR8.SV.neo and JAR trophoblast cells were determined in the presence of hypoxia or normoxia via clonogenic assay. Results BeWo and JAR migration increased by approximately 40% following 24 hour exposure to hypoxia (n=6; BeWo, p<0.05; JAR, p<0.01), and FKBPL protein expression was downregulated (n=3; HTR8.SV.neo, p<0.01; BeWo, p<0.05; JAR, p<0.01), when compared to normoxia. DMOG treatment downregulated FKBPL protein levels in BeWo cells (n=3, p<0.01). JAR colony formation was reduced by approximately 70% in hypoxia (n=3, p<0.01); all colonies appeared to be holoclones. No change in colony formation was observed in HTR8.SV.neo cells; however, there was over two-fold reduction of holoclones, and an increase in differentiated colonies, meroclones plus paraclones (n=3, p<0.05). Conclusion Our in vitro data suggest that FKBPL plays an important role in trophoblast functionality, which may extend to spiral uterine artery remodelling underlying the pathogenesis of pre-eclampsia.
Original languageEnglish
Publication statusPublished - 03 Feb 2018
EventScottish Cardiovascular Forum - Trinity College Dublin
Duration: 03 Feb 201803 Feb 2018

Conference

ConferenceScottish Cardiovascular Forum
Period03/02/201803/02/2018

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Uterine Artery
Pre-Eclampsia
Trophoblasts
Proteins
Down-Regulation
Pathologic Neovascularization
Third Pregnancy Trimester
Type 2 Diabetes Mellitus
Cardiovascular Diseases
Western Blotting
Mothers
Hypertension
Pregnancy
Wounds and Injuries
Hypoxia

Cite this

McNally, R., Todd, N., Alqudah, A., Robson, T., Grieve, D., & McClements, L. (2018). The role of a novel angiogenesis related protein, FKBPL, in spiral uterine artery remodelling important for the pathogenesis of preeclampsia. Abstract from Scottish Cardiovascular Forum, .
McNally, Ross ; Todd, Naomi ; Alqudah, Abdelrahim ; Robson, Tracy ; Grieve, David ; McClements, Lana. / The role of a novel angiogenesis related protein, FKBPL, in spiral uterine artery remodelling important for the pathogenesis of preeclampsia. Abstract from Scottish Cardiovascular Forum, .
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title = "The role of a novel angiogenesis related protein, FKBPL, in spiral uterine artery remodelling important for the pathogenesis of preeclampsia",
abstract = "Introduction Preeclampsia is a complication which occurs in 5{\%}–6{\%} of pregnancies, characterised by high blood pressure and/or other organ dysfunction in the third trimester of pregnancy. Preeclampsia has short-term risks for the mother and child, but is also associated with remote cardiovascular disease and/or type 2 diabetes mellitus in both. The pathogenesis of preeclampsia is unclear but it appears to be attributed to inappropriate remodelling of spiral uterine artery as a result of dysregulated trophoblast function. We investigated the involvement of novel regulator of developmental and pathological angiogenesis, FKBPL, and its role in the pathophysiology of preeclampsia. Methods Trophoblast cells (HTR8.SV.neo, BeWo and JAR) were exposed to hypoxic (1{\%}) or normoxic (21{\%}) conditions before wound scratch migration assays were performed, and FKBPL protein levels measured. BeWo cells were treated with the HIF-1α activator, DMOG, for 24 hour before protein lysates were extracted for western blotting analysis. Colony forming efficiency and the number of holoclones, meroclones and paraclones of both HTR8.SV.neo and JAR trophoblast cells were determined in the presence of hypoxia or normoxia via clonogenic assay. Results BeWo and JAR migration increased by approximately 40{\%} following 24 hour exposure to hypoxia (n=6; BeWo, p<0.05; JAR, p<0.01), and FKBPL protein expression was downregulated (n=3; HTR8.SV.neo, p<0.01; BeWo, p<0.05; JAR, p<0.01), when compared to normoxia. DMOG treatment downregulated FKBPL protein levels in BeWo cells (n=3, p<0.01). JAR colony formation was reduced by approximately 70{\%} in hypoxia (n=3, p<0.01); all colonies appeared to be holoclones. No change in colony formation was observed in HTR8.SV.neo cells; however, there was over two-fold reduction of holoclones, and an increase in differentiated colonies, meroclones plus paraclones (n=3, p<0.05). Conclusion Our in vitro data suggest that FKBPL plays an important role in trophoblast functionality, which may extend to spiral uterine artery remodelling underlying the pathogenesis of pre-eclampsia.",
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year = "2018",
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McNally, R, Todd, N, Alqudah, A, Robson, T, Grieve, D & McClements, L 2018, 'The role of a novel angiogenesis related protein, FKBPL, in spiral uterine artery remodelling important for the pathogenesis of preeclampsia', Scottish Cardiovascular Forum, 03/02/2018 - 03/02/2018.

The role of a novel angiogenesis related protein, FKBPL, in spiral uterine artery remodelling important for the pathogenesis of preeclampsia. / McNally, Ross; Todd, Naomi; Alqudah, Abdelrahim; Robson, Tracy; Grieve, David; McClements, Lana.

2018. Abstract from Scottish Cardiovascular Forum, .

Research output: Contribution to conferenceAbstract

TY - CONF

T1 - The role of a novel angiogenesis related protein, FKBPL, in spiral uterine artery remodelling important for the pathogenesis of preeclampsia

AU - McNally, Ross

AU - Todd, Naomi

AU - Alqudah, Abdelrahim

AU - Robson, Tracy

AU - Grieve, David

AU - McClements, Lana

PY - 2018/2/3

Y1 - 2018/2/3

N2 - Introduction Preeclampsia is a complication which occurs in 5%–6% of pregnancies, characterised by high blood pressure and/or other organ dysfunction in the third trimester of pregnancy. Preeclampsia has short-term risks for the mother and child, but is also associated with remote cardiovascular disease and/or type 2 diabetes mellitus in both. The pathogenesis of preeclampsia is unclear but it appears to be attributed to inappropriate remodelling of spiral uterine artery as a result of dysregulated trophoblast function. We investigated the involvement of novel regulator of developmental and pathological angiogenesis, FKBPL, and its role in the pathophysiology of preeclampsia. Methods Trophoblast cells (HTR8.SV.neo, BeWo and JAR) were exposed to hypoxic (1%) or normoxic (21%) conditions before wound scratch migration assays were performed, and FKBPL protein levels measured. BeWo cells were treated with the HIF-1α activator, DMOG, for 24 hour before protein lysates were extracted for western blotting analysis. Colony forming efficiency and the number of holoclones, meroclones and paraclones of both HTR8.SV.neo and JAR trophoblast cells were determined in the presence of hypoxia or normoxia via clonogenic assay. Results BeWo and JAR migration increased by approximately 40% following 24 hour exposure to hypoxia (n=6; BeWo, p<0.05; JAR, p<0.01), and FKBPL protein expression was downregulated (n=3; HTR8.SV.neo, p<0.01; BeWo, p<0.05; JAR, p<0.01), when compared to normoxia. DMOG treatment downregulated FKBPL protein levels in BeWo cells (n=3, p<0.01). JAR colony formation was reduced by approximately 70% in hypoxia (n=3, p<0.01); all colonies appeared to be holoclones. No change in colony formation was observed in HTR8.SV.neo cells; however, there was over two-fold reduction of holoclones, and an increase in differentiated colonies, meroclones plus paraclones (n=3, p<0.05). Conclusion Our in vitro data suggest that FKBPL plays an important role in trophoblast functionality, which may extend to spiral uterine artery remodelling underlying the pathogenesis of pre-eclampsia.

AB - Introduction Preeclampsia is a complication which occurs in 5%–6% of pregnancies, characterised by high blood pressure and/or other organ dysfunction in the third trimester of pregnancy. Preeclampsia has short-term risks for the mother and child, but is also associated with remote cardiovascular disease and/or type 2 diabetes mellitus in both. The pathogenesis of preeclampsia is unclear but it appears to be attributed to inappropriate remodelling of spiral uterine artery as a result of dysregulated trophoblast function. We investigated the involvement of novel regulator of developmental and pathological angiogenesis, FKBPL, and its role in the pathophysiology of preeclampsia. Methods Trophoblast cells (HTR8.SV.neo, BeWo and JAR) were exposed to hypoxic (1%) or normoxic (21%) conditions before wound scratch migration assays were performed, and FKBPL protein levels measured. BeWo cells were treated with the HIF-1α activator, DMOG, for 24 hour before protein lysates were extracted for western blotting analysis. Colony forming efficiency and the number of holoclones, meroclones and paraclones of both HTR8.SV.neo and JAR trophoblast cells were determined in the presence of hypoxia or normoxia via clonogenic assay. Results BeWo and JAR migration increased by approximately 40% following 24 hour exposure to hypoxia (n=6; BeWo, p<0.05; JAR, p<0.01), and FKBPL protein expression was downregulated (n=3; HTR8.SV.neo, p<0.01; BeWo, p<0.05; JAR, p<0.01), when compared to normoxia. DMOG treatment downregulated FKBPL protein levels in BeWo cells (n=3, p<0.01). JAR colony formation was reduced by approximately 70% in hypoxia (n=3, p<0.01); all colonies appeared to be holoclones. No change in colony formation was observed in HTR8.SV.neo cells; however, there was over two-fold reduction of holoclones, and an increase in differentiated colonies, meroclones plus paraclones (n=3, p<0.05). Conclusion Our in vitro data suggest that FKBPL plays an important role in trophoblast functionality, which may extend to spiral uterine artery remodelling underlying the pathogenesis of pre-eclampsia.

M3 - Abstract

ER -