PSG7 and 9 (Pregnancy‐Specific β‐1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia
Background Preeclampsia is pregnancy specific, involving significant maternal endothelial dysfunction. Predictive biomarkers are lacking. We evaluated the biomarker potential, expression, and function of PSG7 (pregnancy‐specific β‐1 glycoprotein 7) and PSG9 (pregnancy‐specific β‐1 glycoprotein 9) in...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-04-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.121.024536 |
| _version_ | 1797849655662346240 |
|---|---|
| author | Manju Kandel Teresa M. MacDonald Susan P. Walker Catherine Cluver Lina Bergman Jenny Myers Roxanne Hastie Emerson Keenan Natalie J. Hannan Ping Cannon Tuong‐Vi Nguyen Natasha Pritchard Stephen Tong Tu’uhevaha J. Kaitu’u‐Lino |
| author_facet | Manju Kandel Teresa M. MacDonald Susan P. Walker Catherine Cluver Lina Bergman Jenny Myers Roxanne Hastie Emerson Keenan Natalie J. Hannan Ping Cannon Tuong‐Vi Nguyen Natasha Pritchard Stephen Tong Tu’uhevaha J. Kaitu’u‐Lino |
| author_sort | Manju Kandel |
| collection | DOAJ |
| description | Background Preeclampsia is pregnancy specific, involving significant maternal endothelial dysfunction. Predictive biomarkers are lacking. We evaluated the biomarker potential, expression, and function of PSG7 (pregnancy‐specific β‐1 glycoprotein 7) and PSG9 (pregnancy‐specific β‐1 glycoprotein 9) in preeclampsia. Methods and Results At 36 weeks gestation preceding term preeclampsia diagnosis, PSG7 and PSG9 (in Australian cohorts of n=918 and n=979, respectively) were significantly increased before the onset of term preeclampsia (PSG7, P=0.013; PSG9, P=0.0011). In samples collected at 28 to 32 weeks from those with preexisting cardiovascular disease and at high risk of preeclampsia (Manchester Antenatal Vascular Service, UK cohort, n=235), both PSG7 and PSG9 were also significantly increased preceding preeclampsia onset (PSG7, P<0.0001; PSG9, P=0.0003) relative to controls. These changes were validated in the plasma and placentas of patients with established preeclampsia who delivered at <34 weeks gestation (PSG7, P=0.0008; PSG9, P<0.0001). To examine whether PSG7 and PSG9 are associated with increasing disease severity, we measured them in a cohort from South Africa stratified for this outcome, the PROVE (Preeclampsia Obstetric Adverse Events) cohort (n=72). PSG7 (P=0.0027) and PSG9 (P=0.0028) were elevated among patients who were preeclamptic with severe features (PROVE cohort), but not significantly changed in those without severe features or with eclampsia. In syncytialized first trimester cytotrophoblast stem cells, exposure to TNFα (tumor necrosis factor α) or IL‐6 (interleukin 6) significantly increased the expression and secretion of PSG7 and PSG9. In contrast, when we treated primary endothelial cells with recombinant PSG7 and PSG9, we only observed modest changes in Flt‐1 (FMS‐like tyrosine kinase‐1) expression and Plgf (placental growth factor) expression, and no other effects on proangiogenic/antiangiogenic or endothelial dysfunction markers were observed. Conclusions Circulating PSG7 and PSG9 are increased before preeclampsia onset and among those with established disease with their production and release potentially driven by placental inflammation. |
| first_indexed | 2024-04-09T18:47:36Z |
| format | Article |
| id | doaj.art-aac42faf74be4b54aa7c12c44284c57a |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-09T18:47:36Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-aac42faf74be4b54aa7c12c44284c57a2023-04-10T11:57:33ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-04-0111710.1161/JAHA.121.024536PSG7 and 9 (Pregnancy‐Specific β‐1 Glycoproteins 7 and 9): Novel Biomarkers for PreeclampsiaManju Kandel0Teresa M. MacDonald1Susan P. Walker2Catherine Cluver3Lina Bergman4Jenny Myers5Roxanne Hastie6Emerson Keenan7Natalie J. Hannan8Ping Cannon9Tuong‐Vi Nguyen10Natasha Pritchard11Stephen Tong12Tu’uhevaha J. Kaitu’u‐Lino13Translational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaDepartment of Obstetrics and Gynaecology Mercy Hospital for Women University of Melbourne Heidelberg Victoria AustraliaDepartment of Obstetrics and Gynaecology Mercy Hospital for Women University of Melbourne Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaDepartment of Obstetrics and Gynecology Stellenbosch University Cape Town South AfricaDivision of Developmental Biology and Medicine University of ManchesterManchester Academic Health Science CentreSt Mary’s Hospital Manchester United KingdomTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaDepartment of Obstetrics and Gynaecology Mercy Hospital for Women University of Melbourne Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaTranslational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria AustraliaBackground Preeclampsia is pregnancy specific, involving significant maternal endothelial dysfunction. Predictive biomarkers are lacking. We evaluated the biomarker potential, expression, and function of PSG7 (pregnancy‐specific β‐1 glycoprotein 7) and PSG9 (pregnancy‐specific β‐1 glycoprotein 9) in preeclampsia. Methods and Results At 36 weeks gestation preceding term preeclampsia diagnosis, PSG7 and PSG9 (in Australian cohorts of n=918 and n=979, respectively) were significantly increased before the onset of term preeclampsia (PSG7, P=0.013; PSG9, P=0.0011). In samples collected at 28 to 32 weeks from those with preexisting cardiovascular disease and at high risk of preeclampsia (Manchester Antenatal Vascular Service, UK cohort, n=235), both PSG7 and PSG9 were also significantly increased preceding preeclampsia onset (PSG7, P<0.0001; PSG9, P=0.0003) relative to controls. These changes were validated in the plasma and placentas of patients with established preeclampsia who delivered at <34 weeks gestation (PSG7, P=0.0008; PSG9, P<0.0001). To examine whether PSG7 and PSG9 are associated with increasing disease severity, we measured them in a cohort from South Africa stratified for this outcome, the PROVE (Preeclampsia Obstetric Adverse Events) cohort (n=72). PSG7 (P=0.0027) and PSG9 (P=0.0028) were elevated among patients who were preeclamptic with severe features (PROVE cohort), but not significantly changed in those without severe features or with eclampsia. In syncytialized first trimester cytotrophoblast stem cells, exposure to TNFα (tumor necrosis factor α) or IL‐6 (interleukin 6) significantly increased the expression and secretion of PSG7 and PSG9. In contrast, when we treated primary endothelial cells with recombinant PSG7 and PSG9, we only observed modest changes in Flt‐1 (FMS‐like tyrosine kinase‐1) expression and Plgf (placental growth factor) expression, and no other effects on proangiogenic/antiangiogenic or endothelial dysfunction markers were observed. Conclusions Circulating PSG7 and PSG9 are increased before preeclampsia onset and among those with established disease with their production and release potentially driven by placental inflammation.https://www.ahajournals.org/doi/10.1161/JAHA.121.024536biomarkersplacentapreeclampsiapregnancypregnancy specific beta‐1 glycoproteins |
| spellingShingle | Manju Kandel Teresa M. MacDonald Susan P. Walker Catherine Cluver Lina Bergman Jenny Myers Roxanne Hastie Emerson Keenan Natalie J. Hannan Ping Cannon Tuong‐Vi Nguyen Natasha Pritchard Stephen Tong Tu’uhevaha J. Kaitu’u‐Lino PSG7 and 9 (Pregnancy‐Specific β‐1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease biomarkers placenta preeclampsia pregnancy pregnancy specific beta‐1 glycoproteins |
| title | PSG7 and 9 (Pregnancy‐Specific β‐1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia |
| title_full | PSG7 and 9 (Pregnancy‐Specific β‐1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia |
| title_fullStr | PSG7 and 9 (Pregnancy‐Specific β‐1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia |
| title_full_unstemmed | PSG7 and 9 (Pregnancy‐Specific β‐1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia |
| title_short | PSG7 and 9 (Pregnancy‐Specific β‐1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia |
| title_sort | psg7 and 9 pregnancy specific β 1 glycoproteins 7 and 9 novel biomarkers for preeclampsia |
| topic | biomarkers placenta preeclampsia pregnancy pregnancy specific beta‐1 glycoproteins |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.121.024536 |
| work_keys_str_mv | AT manjukandel psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT teresammacdonald psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT susanpwalker psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT catherinecluver psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT linabergman psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT jennymyers psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT roxannehastie psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT emersonkeenan psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT nataliejhannan psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT pingcannon psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT tuongvinguyen psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT natashapritchard psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT stephentong psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia AT tuuhevahajkaituulino psg7and9pregnancyspecificb1glycoproteins7and9novelbiomarkersforpreeclampsia |