Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics

被引：48

作者：

Youssef, Lina ^{[1
,2
]}

Miranda, Jezid ^{[1
,2
]}

Blasco, Miquel ^{[3
]}

Paules, Cristina ^{[1
,2
]}

Crovetto, Francesca ^{[1
,2
]}

Palomo, Marta ^{[4
,5
,6
]}

Torramade-Moix, Sergi ^{[5
]}

Garcia-Caldero, Hector ^{[7
,8
]}

Tura-Ceide, Olga ^{[9
,10
,11
]}

Paula Dantas, Ana ^{[12
]}

Hernandez-Gea, Virginia ^{[7
,8
]}

Herrero, Pol ^{[13
]}

Canela, Nuria ^{[13
]}

Maria Campistol, Josep ^{[3
,14
]}

Carles Garcia-Pagan, Joan ^{[7
,8
]}

Diaz-Ricart, Maribel ^{[5
,6
]}

Gratacos, Eduard ^{[1
,2
,14
,15
]}

Crispi, Fatima ^{[1
,2
,14
]}

机构：

[1] Univ Barcelona, Hosp Clin, BCNatal Fetal Med Res Ctr, Barcelona, Spain

[2] Univ Barcelona, Hosp St Joan Deu, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Barcelona, Spain

[3] Univ Barcelona, Hosp Clin, Ctr Referencia Enfermedad Glomerular Compleja Sis, Nephrol & Renal Transplantat Dept, Barcelona, Spain

[4] Univ Barcelona Campus, Hosp Clin, Josep Carreras Leukaemia Res Inst, Barcelona, Spain

[5] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Ctr Diagnost Biomed CDB,Hematopathol, Barcelona, Spain

[6] Barcelona Endothelium Team BET, Barcelona, Spain

[7] Univ Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Hosp Clin, Liver Unit,Barcelona Hepat Hemodynam Lab, Barcelona, Spain

[8] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Hlth Care Provider European Reference Network Rar, Barcelona, Spain

[9] Univ Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Hosp Clin, Dept Pulm Med, Barcelona, Spain

[10] Biomed Res Networking Ctr Resp Dis CIBERES, Madrid, Spain

[11] Girona Biomed Res Inst IDIBGI, Girona, Spain

[12] Univ Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Hosp Clin, Cardiovasc Inst, Barcelona, Spain

[13] Joint Unit Univ Rovira & Virgili EURECAT, Eurecat, Ctr Tecnol Catalunya, Unique Sci & Tech Infrastruct ICTS,Ctr Omic Sci C, Reus 43204, Spain

[14] Ctr Biomed Res Rare Dis CIBER ER, Madrid, Spain

[15] Hosp Clin Barcelona, Dept Maternal Fetal Med ICGON, Sabino de Arana 1, Barcelona 08028, Spain

来源：

SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期

基金：

芬兰科学院;

关键词：

NORMAL-PREGNANCY; PLATELET ACTIVATION; PULSATILITY INDEX; REFERENCE RANGES; INFLAMMATION; ECULIZUMAB; LEUKOCYTES; WEIGHT; IMMUNE;

D O I：

10.1038/s41598-021-82733-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Preeclampsia is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal morbidity and mortality. The exact pathogenesis of this multifactorial disease remains poorly defined. We applied proteomics analysis on maternal blood samples collected from 14 singleton pregnancies with early-onset severe preeclampsia and 6 uncomplicated pregnancies to investigate the pathophysiological pathways involved in this specific subgroup of preeclampsia. Maternal blood was drawn at diagnosis for cases and at matched gestational age for controls. LC-MS/MS proteomics analysis was conducted, and data were analyzed by multivariate and univariate statistical approaches with the identification of differential pathways by exploring the global human protein-protein interaction network. The unsupervised multivariate analysis (the principal component analysis) showed a clear difference between preeclamptic and uncomplicated pregnancies. The supervised multivariate analysis using orthogonal partial least square discriminant analysis resulted in a model with goodness of fit ((RX)-X-2 = 0.99, p < 0.001) and a strong predictive ability (Q(2)Y = 0.8, p < 0.001). By univariate analysis, we found 17 proteins statistically different after 5% FDR correction (q-value < 0.05). Pathway enrichment analysis revealed 5 significantly enriched pathways whereby the activation of the complement and coagulation cascades was on top (p = 3.17e-07). To validate these results, we assessed the deposits of C5b-9 complement complex and on endothelial cells that were exposed to activated plasma from an independent set of 4 cases of early-onset severe preeclampsia and 4 uncomplicated pregnancies. C5b-9 and Von Willbrand factor deposits were significantly higher in early-onset severe preeclampsia. Future studies are warranted to investigate potential therapeutic targets for early-onset severe preeclampsia within the complement and coagulation pathway.

引用

页数：13

共 74 条

[21] Reference ranges for uterine artery mean pulsatility index at 11-41 weeks of gestation [J].