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

Gaukhar Baidildinova; Vincent Ten Cate; Markus Nagler; Marina Panova-Noeva; Steffen Rapp; Thomas Köck; Jürgen H Prochaska; Stefan Heitmeier; Christoph Gerdes; Stephan Schwers; Stavros V Konstantinides; Thomas Münzel; Christine Espinola-Klein; Karl J Lackner; Henri M N Spronk; Hugo Ten Cate; Paola E J van der Meijden; Kirsten Leineweber; Philipp S Wild; Kerstin Jurk

doi:10.1016/j.thromres.2022.10.005

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

Gaukhar Baidildinova, Vincent Ten Cate, Markus Nagler, Marina Panova-Noeva, Steffen Rapp, Thomas Köck, Jürgen H Prochaska, Stefan Heitmeier, Christoph Gerdes, Stephan Schwers, Stavros V Konstantinides, Thomas Münzel, Christine Espinola-Klein, Karl J Lackner, Henri M N Spronk, Hugo Ten Cate, Paola E J van der Meijden, Kirsten Leineweber, Philipp S Wild, Kerstin Jurk^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

INTRODUCTION: There is evidence that plasma protein profiles differ in the two subtypes of pulmonary embolism (PE), isolated PE (iPE) and deep vein thrombosis (DVT)-associated PE (DVT-PE), in the acute phase. The aim of this study was 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. LASSO-regularized logistic regression analysis selected 33 and 30 of 135 platelet-related candidate proteins in iPE and DVT-PE vs. iDVT, respectively.

RESULTS: All regulated proteins were well associated with six prominently released platelet proteins and the majority showed specificity for iPE and DVT-PE compared to iDVT. While iPE-specific proteins were assigned to be predominantly released via shedding mechanisms and extracellular vesicles, granule secretion 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 linked to tissue remodeling and leukocyte trafficking. Machine learning-based analysis reveals specific plasma signatures and differential release mechanisms of proteins related to platelets in acute iPE and DVT-associated PE.

CONCLUSION: 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.

Original language	English
Pages (from-to)	75-87
Number of pages	13
Journal	Thrombosis Research
Volume	220
DOIs	https://doi.org/10.1016/j.thromres.2022.10.005
Publication status	Published - Dec 2022

Keywords

Humans
Venous Thromboembolism/complications
Prospective Studies
Blood Platelets
Pulmonary Embolism/complications
Acute Disease
Risk Factors

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10.1016/j.thromres.2022.10.005

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Baidildinova, G., Ten Cate, V., Nagler, M., Panova-Noeva, M., Rapp, S., Köck, T., Prochaska, J. H., Heitmeier, S., Gerdes, C., Schwers, S., Konstantinides, S. V., Münzel, T., Espinola-Klein, C., Lackner, K. J., Spronk, H. M. N., Ten Cate, H., van der Meijden, P. E. J., Leineweber, K., Wild, P. S., & Jurk, K. (2022). Subtype-specific plasma signatures of platelet-related protein releasate in acute pulmonary embolism. Thrombosis Research, 220, 75-87. https://doi.org/10.1016/j.thromres.2022.10.005

@article{a47361b0ab2d411b99d7cd1fdac7ac3d,

title = "Subtype-specific plasma signatures of platelet-related protein releasate in acute pulmonary embolism",

abstract = "INTRODUCTION: There is evidence that plasma protein profiles differ in the two subtypes of pulmonary embolism (PE), isolated PE (iPE) and deep vein thrombosis (DVT)-associated PE (DVT-PE), in the acute phase. The aim of this study was 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. LASSO-regularized logistic regression analysis selected 33 and 30 of 135 platelet-related candidate proteins in iPE and DVT-PE vs. iDVT, respectively.RESULTS: All regulated proteins were well associated with six prominently released platelet proteins and the majority showed specificity for iPE and DVT-PE compared to iDVT. While iPE-specific proteins were assigned to be predominantly released via shedding mechanisms and extracellular vesicles, granule secretion 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 linked to tissue remodeling and leukocyte trafficking. Machine learning-based analysis reveals specific plasma signatures and differential release mechanisms of proteins related to platelets in acute iPE and DVT-associated PE.CONCLUSION: 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.",

keywords = "Humans, Venous Thromboembolism/complications, Prospective Studies, Blood Platelets, Pulmonary Embolism/complications, Acute Disease, Risk Factors",

author = "Gaukhar Baidildinova and {Ten Cate}, Vincent and Markus Nagler and Marina Panova-Noeva and Steffen Rapp and Thomas K{\"o}ck and Prochaska, {J{\"u}rgen H} and Stefan Heitmeier and Christoph Gerdes and Stephan Schwers and Konstantinides, {Stavros V} and Thomas M{\"u}nzel and Christine Espinola-Klein and Lackner, {Karl J} and Spronk, {Henri M N} and {Ten Cate}, Hugo and {van der Meijden}, {Paola E J} and Kirsten Leineweber and Wild, {Philipp S} and Kerstin Jurk",

year = "2022",

month = dec,

doi = "10.1016/j.thromres.2022.10.005",

language = "English",

volume = "220",

pages = "75--87",

journal = "Thrombosis Research",

issn = "0049-3848",

publisher = "Elsevier Science",

}

Baidildinova, G, Ten Cate, V, Nagler, M, Panova-Noeva, M, Rapp, S, Köck, T, Prochaska, JH, Heitmeier, S, Gerdes, C, Schwers, S, Konstantinides, SV, Münzel, T, Espinola-Klein, C, Lackner, KJ, Spronk, HMN , Ten Cate, H , van der Meijden, PEJ, Leineweber, K, Wild, PS & Jurk, K 2022, 'Subtype-specific plasma signatures of platelet-related protein releasate in acute pulmonary embolism', Thrombosis Research, vol. 220, pp. 75-87. https://doi.org/10.1016/j.thromres.2022.10.005

TY - JOUR

T1 - Subtype-specific plasma signatures of platelet-related protein releasate in acute pulmonary embolism

AU - Baidildinova, Gaukhar

AU - Ten Cate, Vincent

AU - Nagler, Markus

AU - Panova-Noeva, Marina

AU - Rapp, Steffen

AU - Köck, Thomas

AU - Prochaska, Jürgen H

AU - Heitmeier, Stefan

AU - Gerdes, Christoph

AU - Schwers, Stephan

AU - Konstantinides, Stavros V

AU - Münzel, Thomas

AU - Espinola-Klein, Christine

AU - Lackner, Karl J

AU - Spronk, Henri M N

AU - Ten Cate, Hugo

AU - van der Meijden, Paola E J

AU - Leineweber, Kirsten

AU - Wild, Philipp S

AU - Jurk, Kerstin

PY - 2022/12

Y1 - 2022/12

N2 - INTRODUCTION: There is evidence that plasma protein profiles differ in the two subtypes of pulmonary embolism (PE), isolated PE (iPE) and deep vein thrombosis (DVT)-associated PE (DVT-PE), in the acute phase. The aim of this study was 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. LASSO-regularized logistic regression analysis selected 33 and 30 of 135 platelet-related candidate proteins in iPE and DVT-PE vs. iDVT, respectively.RESULTS: All regulated proteins were well associated with six prominently released platelet proteins and the majority showed specificity for iPE and DVT-PE compared to iDVT. While iPE-specific proteins were assigned to be predominantly released via shedding mechanisms and extracellular vesicles, granule secretion 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 linked to tissue remodeling and leukocyte trafficking. Machine learning-based analysis reveals specific plasma signatures and differential release mechanisms of proteins related to platelets in acute iPE and DVT-associated PE.CONCLUSION: 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.

AB - INTRODUCTION: There is evidence that plasma protein profiles differ in the two subtypes of pulmonary embolism (PE), isolated PE (iPE) and deep vein thrombosis (DVT)-associated PE (DVT-PE), in the acute phase. The aim of this study was 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. LASSO-regularized logistic regression analysis selected 33 and 30 of 135 platelet-related candidate proteins in iPE and DVT-PE vs. iDVT, respectively.RESULTS: All regulated proteins were well associated with six prominently released platelet proteins and the majority showed specificity for iPE and DVT-PE compared to iDVT. While iPE-specific proteins were assigned to be predominantly released via shedding mechanisms and extracellular vesicles, granule secretion 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 linked to tissue remodeling and leukocyte trafficking. Machine learning-based analysis reveals specific plasma signatures and differential release mechanisms of proteins related to platelets in acute iPE and DVT-associated PE.CONCLUSION: 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.

KW - Humans

KW - Venous Thromboembolism/complications

KW - Prospective Studies

KW - Blood Platelets

KW - Pulmonary Embolism/complications

KW - Acute Disease

KW - Risk Factors

U2 - 10.1016/j.thromres.2022.10.005

DO - 10.1016/j.thromres.2022.10.005

M3 - Article

C2 - 36274391

SN - 0049-3848

VL - 220

SP - 75

EP - 87

JO - Thrombosis Research

JF - Thrombosis Research

ER -