Protein expression profiling suggests relevance of noncanonical pathways in isolated pulmonary embolism.

Autor:	Ten Cate V; Preventive Cardiology and Preventive Medicine, Center for Cardiology.; Center for Thrombosis and Hemostasis (CTH), and., Prochaska JH; Preventive Cardiology and Preventive Medicine, Center for Cardiology.; Center for Thrombosis and Hemostasis (CTH), and.; German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany., Schulz A; Preventive Cardiology and Preventive Medicine, Center for Cardiology., Koeck T; Preventive Cardiology and Preventive Medicine, Center for Cardiology., Pallares Robles A; Center for Thrombosis and Hemostasis (CTH), and., Lenz M; Preventive Cardiology and Preventive Medicine, Center for Cardiology.; Institute of Organismic and Molecular Evolution, Johannes Gutenberg University Mainz, Mainz, Germany., Eggebrecht L; Preventive Cardiology and Preventive Medicine, Center for Cardiology.; Center for Thrombosis and Hemostasis (CTH), and., Rapp S; Preventive Cardiology and Preventive Medicine, Center for Cardiology., Panova-Noeva M; Preventive Cardiology and Preventive Medicine, Center for Cardiology.; Center for Thrombosis and Hemostasis (CTH), and.; German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany., Ghofrani HA; University Hospital Gießen and Marburg, Ambulance for Pulmonary Hypertension, Gießen, Germany., Meyer FJ; Lung Center Munich, Department of Pneumology and Pneumological Oncology, München Klinik Bogenhausen, München, Germany., Espinola-Klein C; Department of Angiology., Lackner KJ; Institute of Clinical Chemistry and Laboratory Medicine., Michal M; Department of Psychosomatic Medicine and Psychotherapy., Schuster AK; Department of Ophthalmology, and., Strauch K; Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany., Zink AM; Bayer AG, Wuppertal, Germany., Laux V; Bayer AG, Wuppertal, Germany., Heitmeier S; Bayer AG, Wuppertal, Germany., Konstantinides SV; Center for Thrombosis and Hemostasis (CTH), and.; Department of Cardiology, Democritus University of Thrace, University General Hospital, Greece; and., Münzel T; Center for Thrombosis and Hemostasis (CTH), and.; German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.; Center for Cardiology - Cardiology I, University Medical Center of the Johannes Gutenberg University, Mainz, Germany., Andrade-Navarro MA; Institute of Organismic and Molecular Evolution, Johannes Gutenberg University Mainz, Mainz, Germany., Leineweber K; Bayer AG, Wuppertal, Germany., Wild PS; Preventive Cardiology and Preventive Medicine, Center for Cardiology.; Center for Thrombosis and Hemostasis (CTH), and.; German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2021 May 13; Vol. 137 (19), pp. 2681-2693.
DOI:	10.1182/blood.2019004571
Abstrakt:	Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism Project, a multicenter prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE patients (n = 96) against those of patients with DVT-associated PE (n = 276) or isolated DVT (n = 160). This resulted in the identification of shared molecular processes between PE phenotypes, as well as an isolated PE-specific protein signature. Shared processes included upregulation of inflammation, response to oxidative stress, and the loss of pulmonary surfactant. The isolated PE-specific signature consisted of 5 proteins: interferon-γ, glial cell line-derived neurotrophic growth factor, polypeptide N-acetylgalactosaminyltransferase 3, peptidyl arginine deiminase type-2, and interleukin-15 receptor subunit α. These proteins were orthogonally validated using cis protein quantitative trait loci. External replication in an independent population-based cohort (n = 5778) further validated the proteomic results and showed that they were prognostic for incident primary isolated PE in individuals without history of VTE (median time to event: 2.9 years; interquartile range: 1.6-4.2 years), supporting their possible involvement in the early pathogenesis. This study has identified molecular overlaps and differences between VTE phenotypes. In particular, the results implicate noncanonical pathways more commonly associated with respiratory and atherosclerotic disease in the acute pathophysiology of isolated PE. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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