Dataset Information

Plasma fibrin clot-bound proteins in antiphospholipid syndrome and venous thromboembolism: relation with inflammation and thrombosis

ABSTRACT: Antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis. The unfavorable fibrin clot phenotype, including formation of dense and poorly lysable clots, has been reported both in thrombotic APS and venous thromboembolism (VTE). The presence and amount of different proteins within a plasma clot, not only associated with the coagulation system, may influence clot properties. To our knowledge, there is a lack of data on plasma fibrin-clot bound proteins in patients with thrombotic APS or VTE. The aim of our study was to perform a quantitative proteomic analysis of fibrin clots prepared from citrated plasma from subjects with thrombotic APS and prior VTE, along with fibrin clot permeability (Ks) and clot lysis time (CLT) assessed ex vivo. We investigated 23 consecutive patients with APS, 18 with a history of first-ever VTE, and 20 age and sex matched healthy subjects. A multiple enzyme digestion filter aided sample preparation and a multienzyme digestion (MED) FASP method combined with LC-MS/MS analysis performed on a Proxeon Easy-nLC System coupled to the Q Exactive HF mass spectrometer were used. The proteomic analysis revealed that clot composition regarding 117 proteins in APS patients and 48 proteins in VTE patients was changed as compared to healthy controls, while 72 clot-bounded proteins differed between APS and VTE subjects. In healthy controls, Ks was associated with fibrinogen alpha and gamma chains (r=0.46 and r=0.46, both p<0.05, respectively) or apolipoprotein B-100 (r=-0.53, p<0.05), while CLT correlated with annexin A2 (r=-0.58, p<0.05), apolipoportein(a) (r=0.47, p<0.05), or platelet glycoprotein 4 (r=0.59, p<0.05). In VTE patients correlations of Ks with complement C1q and histone H2B, as factors closely linked with thrombosis, were observed (r=-0.52 and r=-0.47, both p<0.05, respectively). In patients with thrombotic APS all above-mentioned associations were not found. This study is the first to show that different proteins are able to influence the clot formation, structure, and properties. Since, prothrombotic conditions abolished associations observed in healthy subjects fibrin clots, differences in protein clot components might explain the links between prothrombotic fibrin clot phenotype and thromboembolic events.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Jacek Wisniewski

LAB HEAD: Jacek R Wisniewski

PROVIDER: PXD008434 | Pride | 2019-08-20

REPOSITORIES: Pride

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			Action	DRS
	20170123_QEp7_JRW_SA_CT_Z1.raw	Raw
	20170123_QEp7_JRW_SA_CT_Z2.raw	Raw
	20170123_QEp7_JRW_SA_CT_Z29.raw	Raw
	20170123_QEp7_JRW_SA_CT_Z3.raw	Raw
	20170123_QEp7_JRW_SA_CT_Z30.raw	Raw

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Plasma fibrin clot proteomics in healthy subjects: Relation to clot permeability and lysis time.

Ząbczyk Michał M Stachowicz Aneta A Natorska Joanna J Olszanecki Rafał R Wiśniewski Jacek R JR Undas Anetta A

Journal of proteomics 20190816

<h4>Background</h4>Little is known about fibrin clot composition in relation to its structure and lysability. We investigated plasma clots protein composition and its associations with clot properties.<h4>Methods</h4>We studied 20 healthy subjects aged 31-49 years in whom plasma fibrin clot permeability (K<sub>s</sub>) and clot lysis time (CLT) were determined. A proteomic analysis of plasma fibrin clots was based on quantitative liquid chromatography-mass spectrometry.<h4>Results</h4>Among 494 ...[more]

PMID: 31425886

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Project description:Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. We studied 134 patients with VTE separated into 3 groups: (1) âlow-riskâ patients had â¥1 provoked VTE; (2) âmoderate-riskâ patients had no more than 1 unprovoked VTE; (3) âhigh-riskâ patients had â¥2 unprovoked VTE. 44 individuals with no history of VTE were enrolled as healthy controls. Consented individuals were enrolled at 4 medical centers in the US. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Using class prediction analysis, we distinguished high-risk patients from healthy controls with good receiver operating curve characteristics (AUC=0.88). We also distinguished high-risk from low-risk individuals, moderate-risk individuals from healthy controls, and low-risk individuals from healthy controls with AUCâs of 0.72, 0.77 and 0.72, respectively. Using differential expression analysis, we identified genes relevant to coagulation, immune response and vascular biology, such as SELP and CD46, which were differentially expressed in at least two comparisons. Neither approach distinguished the moderate-risk patients from the high-risk or low-risk groups. Gene expression profiles may provide insights into biological mechanisms associated with patients at risk for recurrent VTE. Prospective studies are needed to validate these findings. This study includes a total of 218 samples/individuals (in 5 groups; APS, high-risk VTE, moderate-risk VTE, low-risk VTE and healthy-controls). Samples in which the percent of probes present was 15% or less (n=51) were excluded leaving 167 samples. The data for these 167 samples were normalized together. However, this record represents the 132 individual samples in the following groups; high-risk (n=40); moderate-risk (n=33); low-risk (n=34); and healthy controls (n=25). The 35 samples in APS group are represented in GSE48001.