PXD031521

PXD031521 is an original dataset announced via ProteomeXchange.

Title	An evolutionary conserved, immobility associated antithrombotic mechanism
Description	Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a main cause of morbidity and mortality that causes tremendous health care costs. Short term immobility related conditions arising from hospitalization, acute trauma and forced bed rest are major risk factors for the development of VTE. In contrast, chronically paralyzed patients with post-spinal cord injury are protected from VTE despite immobilization. Similarly, free-ranging brown bears (Ursus arctos) that hibernate (immobilize) have adapted to this threat through yet to be discovered mechanisms and do not develop VTE. This suggests that long-term immobility can induce antithrombotic mechanisms that are evolutionarily conserved. Here we aimed to identify these adaptive mechanisms of VTE protection in a cross-species approach. Mass spectrometry-based proteomics identified platelet expressed heat shock protein 47 (Hsp47) as the most substantially downregulated protein during brown bear hibernation. In a clinical bed rest study and in spinal-cord injured humans, we likewise observed drastic reduction of platelet-expressed Hsp47. Genetic ablation and pharmaceutical inhibition of platelet Hsp47 attenuates deep vein thrombosis and thromboinflammatory responses in mice and human blood cells. This suggests that Hsp47 downregulation is an evolutionarily conserved mechanism that also protects immobilized patients from VTE. Our translational approach thus identified an antithrombotic signature that may give rise to novel antithrombotic therapeutics and prognostic markers.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:44:44.371.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-09 05:02:06	ID requested
1	2023-04-14 00:10:26	announced
2	2023-11-14 08:55:54	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:44:44	announced	2024-10-22: Updated project metadata.

10.1126/SCIENCE.ABO5044;

submitter keyword: VTE,Platelets

Matthias Mann
contact affiliation	Director at Max Planck Institute of Biochemistry Department Proteomics und Signaltransduktion Am Klopferspitz 18, 82152 Martinsried
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031521
     1. Label: PRIDE project
     2. Name: An evolutionary conserved, immobility associated antithrombotic mechanism