VPB0372 - Subtype-specific plasma signatures of platelet-related protein releasate in acute pulmonary embolism

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Gaukhar Baidildinova, MRes

PhD student
Maastricht University
Mainz, Rheinland-Pfalz, Germany

Co-Author(s)

Vt

Vincent ten Cate

Postdoc
Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz (UMCM), Mainz, Germany
Mainz, Rheinland-Pfalz, Germany
MN

Markus Nagler

Statistician
Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz
Mainz, Rheinland-Pfalz, Germany
MP

Marina Panova-Noeva

Junior group leader
Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
mainz, Rheinland-Pfalz, Germany
SR

Steffen Rapp

Head of research laboratory
2 Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
Mainz, Rheinland-Pfalz, Germany
TK

Thomas Koeck

Head of laboratory
Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Mainz, Rheinland-Pfalz, Germany
JP

Jürgen Prochaska

Head Junior Research Group Clinical Epidemiology and Systems Medicine
Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
Mainz, Rheinland-Pfalz, Germany
SH

Stefan Heitmeier

Principal Scientist
Bayer AG, Wuppertal, Germany
Wuppertal, Nordrhein-Westfalen, Germany
CG

Christoph Gerdes

Senior Scientist
Bayer AG
Wuppertal, Nordrhein-Westfalen, Germany
SS

Stephan Schwers

Principal Scientist
Bayer AG
Wuppertal, Nordrhein-Westfalen, Germany
SK

Stavros Konstantinides

MD, PhD
Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University
Mainz, Rheinland-Pfalz, Germany
TM

Thomas Münzel

Professor, Head of Cardiology I Department
Center for Cardiology - Cardiology I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
Mainz, Rheinland-Pfalz, Germany
CE

Christine Espinola-Klein

Professor, Head of Angiology Department
Center for Cardiology, Cardiology III - Angiology; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz
mainz, Rheinland-Pfalz, Germany
KL

Karl Lackner

Professor, Head of the Institute for Clinical Chemistry and Laboratory Medicine
Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
mainz, Rheinland-Pfalz, Germany
HS

Henri M.H. Spronk

Chief Executive Officer
Coagulation Profile, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Hugo ten Cate, MD, PhD, FAHA

Professor, MD, PhD
Thrombosis Expertise Center, Heart & Vascular Center, Maastricht University Medical Center, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Paola van der Meijden, PhD

Assistant Professor
Department of Biochemistry, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
KL

Kirsten Leineweber

Head Disease Genomics
Bayer AG
Wuppertal, Nordrhein-Westfalen, Germany
PS

Philipp S. S. Wild

Professor
Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz (UMCM), Mainz, Germany
Mainz, Rheinland-Pfalz, Germany
Kerstin Jurk, PhD

Professor
Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University, Mainz, Germany
Mainz, Rheinland-Pfalz, Germany

Background: Recent evidence suggests that the two subtypes of pulmonary embolism (PE), isolated PE (iPE) and deep vein thrombosis (DVT)-associated PE (DVT-PE) differ in terms of plasma protein profiles in the acute phase.

Aims: This study aimed to determine specific plasma signatures for proteins related to platelets in acute iPE and DVT-PE compared to isolated DVT (iDVT).

Methods: Within the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism (GMP-VTE) Project, a multicenter prospective cohort study of 693 confirmed VTE cases, a highly sensitive targeted proteomics approach based on dual-antibody proximity extension assay was applied. Whole leg ultrasonography was performed to exclude DVT in individuals with iPE. This study was approved by the local Ethics committee including signed patient informed consent. A total of 135 platelet-related candidate proteins were selected from 444 proteins according to mass spectrometry-based platelet proteomics databases and a systematic literature screen. LASSO-regularized logistic regression models were utilized for analysis of regulated proteins.

Results: LASSO-analysis selected 33 and 30 of 135 platelet-related proteins in iPE and DVT-PE vs. iDVT, respectively. The majority of the selected proteins did not overlap between PE-subtypes. While iPE-specific proteins were assigned to be predominantly released via shedding mechanisms and extracellular vesicles, degranulation was identified as a major release mechanism assigned to DVT-associated PE-specific proteins. Network analysis demonstrated three interconnected clusters of specifically regulated proteins in iPE linked to immunoreceptor signaling, pathogen clearance and chemotaxis, whereas for DVT-associated PE one cluster was linked to tissue remodeling and leukocyte trafficking.

Conclusion(s): Machine learning-based analysis revealed specific plasma signatures and differential release mechanisms of proteins related to platelets in iPE and DVT- PE. These data suggest that the platelet protein releasate contributes to the differential regulation of plasma proteins in acute PE compared to iDVT, which may be associated with different platelet activation patterns.
GB is supported by EU-TICARDIO No. 813409.