Platelets in preeclampsia: an observational study of indices associated with aspirin nonresponsiveness, activation and transcriptional landscape
Abstract Background Platelets play critical roles in the pathogenesis of preeclampsia, including thrombosis, endothelial dysfunction and inflammation. However, preeclampsia-associated changes in platelet gene expression and activation at the maternal–foetal interface remain unknown. Moreover, aspiri...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | BMC Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12916-025-04132-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849335670916513792 |
|---|---|
| author | Gashaw Garedew Woldeamanuel Kenean Getaneh Tlaye Xueqin Wang Long Nguyen-Hoang Qiongjie Zhou Yinan Wang Bo Wah Leung Yao Wang Liona C. Poon Chi Chiu Wang |
| author_facet | Gashaw Garedew Woldeamanuel Kenean Getaneh Tlaye Xueqin Wang Long Nguyen-Hoang Qiongjie Zhou Yinan Wang Bo Wah Leung Yao Wang Liona C. Poon Chi Chiu Wang |
| author_sort | Gashaw Garedew Woldeamanuel |
| collection | DOAJ |
| description | Abstract Background Platelets play critical roles in the pathogenesis of preeclampsia, including thrombosis, endothelial dysfunction and inflammation. However, preeclampsia-associated changes in platelet gene expression and activation at the maternal–foetal interface remain unknown. Moreover, aspirin nonresponsiveness in high-risk pregnancies underscores the need for low-cost biomarkers to identify nonresponders. Nevertheless, the changes of platelet indices in women who develop preeclampsia despite aspirin prophylaxis have not yet been evaluated. In this study, we aimed to investigate the changes in platelet indices associated with aspirin nonresponsiveness, activation state and transcriptional landscape in preeclampsia. Methods Platelet indices were compared between aspirin-responsive and nonresponsive women. Logistic regression analysis was performed to determine the associations between platelet indices and aspirin nonresponsiveness. Opal immunofluorescence staining was performed to evaluate the expression of platelet-specific (CD42b) and activation (CD62P) markers in placental villous and decidual tissues. RNA sequencing (RNA-seq) was performed to investigate the transcriptomic profile of platelets. Results A decrease in platelet count (PC) during the second trimester as well as an increase in mean platelet volume (MPV) and a lower PC/MPV ratio in the third trimester were significantly associated with the subsequent development of aspirin nonresponsiveness. We observed significantly greater expression of CD62P in the placental villous and CD42b in the decidua of the preeclamptic group than in those of the nonpreeclamptic group. Colocalization analysis of CD42b and CD62P revealed that the preeclamptic placenta and decidua presented significant platelet activation. RNA-seq analysis revealed a total of 20, 618 and 1819 transcripts in the peripheral blood, placental villous and decidua of preeclamptic women, respectively. Functional analysis revealed that the PI3K-Akt and Wnt signalling pathways were significantly enriched in the placental villous and decidua of preeclamptic patients, respectively. RT‒qPCR analysis confirmed the upregulation of FKBP5, LAMA5, FZD5 and FGG mRNA expression in preeclampsia. Conclusions Our findings suggest that PC in the second trimester and PC, MPV and PC/MPV ratio in the third trimester may be useful for assessing aspirin nonresponsiveness in women at high risk of preeclampsia. Furthermore, our findings demonstrate that preeclampsia is associated with increased platelet activation and significant enrichment of signalling pathways involved in platelet activation. |
| format | Article |
| id | doaj-art-543635d341dc4c81a4f28f565250f2db |
| institution | Kabale University |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj-art-543635d341dc4c81a4f28f565250f2db2025-08-20T03:45:11ZengBMCBMC Medicine1741-70152025-06-0123112010.1186/s12916-025-04132-9Platelets in preeclampsia: an observational study of indices associated with aspirin nonresponsiveness, activation and transcriptional landscapeGashaw Garedew Woldeamanuel0Kenean Getaneh Tlaye1Xueqin Wang2Long Nguyen-Hoang3Qiongjie Zhou4Yinan Wang5Bo Wah Leung6Yao Wang7Liona C. Poon8Chi Chiu Wang9Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Obstetrics, Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Obstetrics, Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong KongAbstract Background Platelets play critical roles in the pathogenesis of preeclampsia, including thrombosis, endothelial dysfunction and inflammation. However, preeclampsia-associated changes in platelet gene expression and activation at the maternal–foetal interface remain unknown. Moreover, aspirin nonresponsiveness in high-risk pregnancies underscores the need for low-cost biomarkers to identify nonresponders. Nevertheless, the changes of platelet indices in women who develop preeclampsia despite aspirin prophylaxis have not yet been evaluated. In this study, we aimed to investigate the changes in platelet indices associated with aspirin nonresponsiveness, activation state and transcriptional landscape in preeclampsia. Methods Platelet indices were compared between aspirin-responsive and nonresponsive women. Logistic regression analysis was performed to determine the associations between platelet indices and aspirin nonresponsiveness. Opal immunofluorescence staining was performed to evaluate the expression of platelet-specific (CD42b) and activation (CD62P) markers in placental villous and decidual tissues. RNA sequencing (RNA-seq) was performed to investigate the transcriptomic profile of platelets. Results A decrease in platelet count (PC) during the second trimester as well as an increase in mean platelet volume (MPV) and a lower PC/MPV ratio in the third trimester were significantly associated with the subsequent development of aspirin nonresponsiveness. We observed significantly greater expression of CD62P in the placental villous and CD42b in the decidua of the preeclamptic group than in those of the nonpreeclamptic group. Colocalization analysis of CD42b and CD62P revealed that the preeclamptic placenta and decidua presented significant platelet activation. RNA-seq analysis revealed a total of 20, 618 and 1819 transcripts in the peripheral blood, placental villous and decidua of preeclamptic women, respectively. Functional analysis revealed that the PI3K-Akt and Wnt signalling pathways were significantly enriched in the placental villous and decidua of preeclamptic patients, respectively. RT‒qPCR analysis confirmed the upregulation of FKBP5, LAMA5, FZD5 and FGG mRNA expression in preeclampsia. Conclusions Our findings suggest that PC in the second trimester and PC, MPV and PC/MPV ratio in the third trimester may be useful for assessing aspirin nonresponsiveness in women at high risk of preeclampsia. Furthermore, our findings demonstrate that preeclampsia is associated with increased platelet activation and significant enrichment of signalling pathways involved in platelet activation.https://doi.org/10.1186/s12916-025-04132-9PlateletsPreeclampsiaAspirinTranscriptome |
| spellingShingle | Gashaw Garedew Woldeamanuel Kenean Getaneh Tlaye Xueqin Wang Long Nguyen-Hoang Qiongjie Zhou Yinan Wang Bo Wah Leung Yao Wang Liona C. Poon Chi Chiu Wang Platelets in preeclampsia: an observational study of indices associated with aspirin nonresponsiveness, activation and transcriptional landscape BMC Medicine Platelets Preeclampsia Aspirin Transcriptome |
| title | Platelets in preeclampsia: an observational study of indices associated with aspirin nonresponsiveness, activation and transcriptional landscape |
| title_full | Platelets in preeclampsia: an observational study of indices associated with aspirin nonresponsiveness, activation and transcriptional landscape |
| title_fullStr | Platelets in preeclampsia: an observational study of indices associated with aspirin nonresponsiveness, activation and transcriptional landscape |
| title_full_unstemmed | Platelets in preeclampsia: an observational study of indices associated with aspirin nonresponsiveness, activation and transcriptional landscape |
| title_short | Platelets in preeclampsia: an observational study of indices associated with aspirin nonresponsiveness, activation and transcriptional landscape |
| title_sort | platelets in preeclampsia an observational study of indices associated with aspirin nonresponsiveness activation and transcriptional landscape |
| topic | Platelets Preeclampsia Aspirin Transcriptome |
| url | https://doi.org/10.1186/s12916-025-04132-9 |
| work_keys_str_mv | AT gashawgaredewwoldeamanuel plateletsinpreeclampsiaanobservationalstudyofindicesassociatedwithaspirinnonresponsivenessactivationandtranscriptionallandscape AT keneangetanehtlaye plateletsinpreeclampsiaanobservationalstudyofindicesassociatedwithaspirinnonresponsivenessactivationandtranscriptionallandscape AT xueqinwang plateletsinpreeclampsiaanobservationalstudyofindicesassociatedwithaspirinnonresponsivenessactivationandtranscriptionallandscape AT longnguyenhoang plateletsinpreeclampsiaanobservationalstudyofindicesassociatedwithaspirinnonresponsivenessactivationandtranscriptionallandscape AT qiongjiezhou plateletsinpreeclampsiaanobservationalstudyofindicesassociatedwithaspirinnonresponsivenessactivationandtranscriptionallandscape AT yinanwang plateletsinpreeclampsiaanobservationalstudyofindicesassociatedwithaspirinnonresponsivenessactivationandtranscriptionallandscape AT bowahleung plateletsinpreeclampsiaanobservationalstudyofindicesassociatedwithaspirinnonresponsivenessactivationandtranscriptionallandscape AT yaowang plateletsinpreeclampsiaanobservationalstudyofindicesassociatedwithaspirinnonresponsivenessactivationandtranscriptionallandscape AT lionacpoon plateletsinpreeclampsiaanobservationalstudyofindicesassociatedwithaspirinnonresponsivenessactivationandtranscriptionallandscape AT chichiuwang plateletsinpreeclampsiaanobservationalstudyofindicesassociatedwithaspirinnonresponsivenessactivationandtranscriptionallandscape |