{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:43:50Z","timestamp":1787064230996,"version":"build-2736575974"},"reference-count":108,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Platelets may be pivotal mediators of the thrombotic and coagulopathic complications of preeclampsia (PE), linking inflammation and thrombosis with endothelial and vascular dysfunction. Both PE and gestational hypertension (GH) fall within the spectrum of hypertensive complications of pregnancy, with GH being a risk factor for preeclampsia. However, it is unclear what biomarkers distinguish PE from GH. Using a discovery size cohort, we aimed to characterize specific plasma and platelet thrombo-inflammatory drivers indicative of PE and differentiate PE from GH. We performed multiplex immunoassays, platelet and plasma quantitative proteomics and metabolomics of PE patients, comparing with non-pregnant (NP), healthy pregnant controls (PC) and GH participants. The expression pattern of plasma proteins and metabolites in PE\/GH platelets was distinct from that of NP and PC. Whilst procoagulation in PC may be fibrinogen driven, inter-alpha-trypsin inhibitors ITIH2 and ITIH3 are likely mediators of thrombo-inflammation in GH and PE, and fibronectin and S100A8\/9 may be major procoagulant agonists in PE only. Also enriched in PE were CCL1 and CCL27 plasma cytokines, and the platelet leucine-rich repeat-containing protein 27 and 42 (LRRC27\/42), whose effects on platelets were explored using STRING analysis. Through protein-protein interactions analysis, we generated a new hypothesis for platelets\u2019 contribution to the thrombo-inflammatory states of preeclampsia.<\/jats:p>","DOI":"10.3390\/cells11081256","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T13:39:51Z","timestamp":1649338791000},"page":"1256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Proteomics and Metabolomics Profiling of Platelets and Plasma Mediators of Thrombo-Inflammation in Gestational Hypertension and Preeclampsia"],"prefix":"10.3390","volume":"11","author":[{"given":"Luiz Gustavo N.","family":"de Almeida","sequence":"first","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Young","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Perioperative and Pain Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Nicholas","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Perioperative and Pain Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne","family":"Lee","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute, Calgary, AB T2N 1N4, Canada"},{"name":"Division of Hematology, Department of Medicine\/Medical Oncology, University of British Columbia, Island Health, Victoria, BC V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7012-2420","authenticated-orcid":false,"given":"Man-Chiu","family":"Poon","sequence":"additional","affiliation":[{"name":"Division of Hematology & Hematological Malignancies, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-4188","authenticated-orcid":false,"given":"Antoine","family":"Dufour","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0043-9115","authenticated-orcid":false,"given":"Ejaife O.","family":"Agbani","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute, Calgary, AB T2N 1N4, Canada"},{"name":"Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S1701-2163(15)30588-0","article-title":"Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary","volume":"36","author":"Magee","year":"2014","journal-title":"J. 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