# Proteomic Insights into Venous Thromboembolism

**Authors:** Oana-Mădălina Manole, Brîndușa Alina Petre, Viviana Onofrei

PMC · DOI: 10.3390/medsci14010094 · Medical Sciences · 2026-02-15

## TL;DR

This paper reviews how proteomics can improve understanding and diagnosis of venous thromboembolism by identifying key proteins and pathways involved.

## Contribution

The paper provides a synthesis of proteomic studies on VTE, highlighting novel biomarkers and distinct molecular signatures between PE and DVT.

## Key findings

- Proteomic profiling reveals consistent alterations in coagulation, inflammation, and endothelial dysfunction pathways in VTE.
- Distinct molecular signatures between isolated PE and DVT suggest biologically heterogeneous VTE phenotypes.
- Proteomic data integration with clinical and genetic information may advance precision medicine for VTE.

## Abstract

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), remains a major cause of morbidity and mortality worldwide, with significant clinical challenges in diagnosis and risk stratification. Traditional diagnostic tools, including clinical prediction scores, D-dimer testing, and imaging, are limited by suboptimal specificity or sensitivity. In this context, proteomics-based approaches have emerged as powerful tools to elucidate the molecular mechanisms of VTE and to identify novel diagnostic and prognostic biomarkers. This review synthesizes recent advances in proteomic research relevant to VTE. We searched four databases (PubMed, ScienceDirect, Springer Nature, and Wiley) using the keywords “acute pulmonary embolism”, “acute venous thromboembolism”, and “proteomics”. Thirty proteomic studies investigating VTE were examined. Across these studies, proteomic profiling consistently revealed alterations in pathways related to coagulation, inflammation, platelet activation, endothelial dysfunction, and fibrin clot structure. Multiple protein classes, including acute-phase reactants, complement components, coagulation factors, and platelet-derived proteins, have demonstrated potential value in improving diagnostic accuracy and refining prognostic stratification. Proteomic analyses have also revealed distinct molecular signatures between isolated PE and isolated DVT, supporting the concept of biologically heterogeneous VTE phenotypes. Furthermore, emerging evidence from COVID-19–associated thrombosis, cancer-associated VTE, and non-invasive sources such as exhaled breath condensate underscores the expanding clinical relevance of proteomic approaches. Although technical limitations and heterogeneity across studies remain challenges, the integration of proteomic data with clinical and genetic information holds promise for advancing precision medicine in VTE.

## Linked entities

- **Diseases:** Venous thromboembolism (MONDO:0005399), pulmonary embolism (MONDO:0005279)

## Full-text entities

- **Genes:** PEBP1 (phosphatidylethanolamine binding protein 1) [NCBI Gene 5037] {aka HCNP, HCNPpp, HEL-210, HEL-S-34, HEL-S-96, PBP}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, F12 (coagulation factor XII) [NCBI Gene 2161] {aka HAE3, HAEX, HAF}, LGALS4 (galectin 4) [NCBI Gene 3960] {aka GAL4, L36LBP}, ACTG1 (actin gamma 1) [NCBI Gene 71] {aka ACT, ACTG, DFNA20, DFNA26, HEL-176}, CLEC4C (C-type lectin domain family 4 member C) [NCBI Gene 170482] {aka BDCA-2, BDCA2, CD303, CLECSF11, CLECSF7, DLEC}, H1-5 (H1.5 linker histone, cluster member) [NCBI Gene 3009] {aka H1, H1.5, H1B, H1F5, H1s-3, HIST1H1B}, CTSD (cathepsin D) [NCBI Gene 1509] {aka CLN10, CPSD, HEL-S-130P}, AVP (arginine vasopressin) [NCBI Gene 551] {aka ADH, ARVP, AVP-NPII, AVRP, VP}, RPLP2 (ribosomal protein lateral stalk subunit P2) [NCBI Gene 6181] {aka D11S2243E, LP2, P2, RPP2}, WDR59 (WD repeat domain 59) [NCBI Gene 79726] {aka CDW12, FP977, p90-120}, SCGB3A2 (secretoglobin family 3A member 2) [NCBI Gene 117156] {aka LU103, PNSP1, UGRP1, pnSP-1}, VTN (vitronectin) [NCBI Gene 7448] {aka V75, VN, VNT}, CSDE1 (cold shock domain containing E1) [NCBI Gene 7812] {aka D1S155E, UNR}, SERPINC1 (serpin family C member 1) [NCBI Gene 462] {aka AT3, AT3D, ATIII, ATIII-R2, ATIII-T1, ATIII-T2}, KRT9 (keratin 9) [NCBI Gene 3857] {aka CK-9, EPPK, K9}, SELP (selectin P) [NCBI Gene 6403] {aka CD62, CD62P, GMP140, GRMP, LECAM3, PADGEM}, PDGFB (platelet derived growth factor subunit B) [NCBI Gene 5155] {aka IBGC5, PDGF-2, PDGF2, SIS, SSV, c-sis}, ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) [NCBI Gene 3700] {aka GP120, H4P, IHRP, ITI-HC4, ITIHL1, PK-120}, CLU (clusterin) [NCBI Gene 1191] {aka AAG4, APO-J, APOJ, CLI, CLU1, CLU2}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, IGHA1 (immunoglobulin heavy constant alpha 1) [NCBI Gene 3493] {aka IgA1}, IL17C (interleukin 17C) [NCBI Gene 27189] {aka CX2, IL-17C}, DGKZ (diacylglycerol kinase zeta) [NCBI Gene 8525] {aka DAGK5, DAGK6, DGK-ZETA, hDGKzeta}, PIP (prolactin induced protein) [NCBI Gene 5304] {aka BRST-2, GCDFP-15, GCDFP15, GPIP4}, MAN1A2 (mannosidase alpha class 1A member 2) [NCBI Gene 10905] {aka MAN1B}, PGLYRP1 (peptidoglycan recognition protein 1) [NCBI Gene 8993] {aka PGLYRP, PGRP, PGRP-S, PGRPS, TAG7, TNFSF3L}, APOH (apolipoprotein H) [NCBI Gene 350] {aka B2G1, B2GP1, BG}, SAA4 (serum amyloid A4, constitutive) [NCBI Gene 6291] {aka C-SAA, CSAA}, TNC (tenascin C) [NCBI Gene 3371] {aka 150-225, DFNA56, GMEM, GP, HXB, JI}, TTR (transthyretin) [NCBI Gene 7276] {aka AMYLD1, ATTR, CTS, CTS1, HEL111, HsT2651}, AZGP1 (alpha-2-glycoprotein 1, zinc-binding) [NCBI Gene 563] {aka ZA2G, ZAG}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, LRRC15 (leucine rich repeat containing 15) [NCBI Gene 131578] {aka LIB}, DBP (D-box binding PAR bZIP transcription factor) [NCBI Gene 1628] {aka DABP, taxREB302}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, FABP4 (fatty acid binding protein 4) [NCBI Gene 2167] {aka A-FABP, AFABP, ALBP, HEL-S-104, aP2}, PLAUR (plasminogen activator, urokinase receptor) [NCBI Gene 5329] {aka CD87, U-PAR, UPAR, URKR}, ANGPTL4 (angiopoietin like 4) [NCBI Gene 51129] {aka ARP4, FIAF, HARP, HFARP, NL2, PGAR}, CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919] {aka FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3}, NCCRP1 (NCCRP1, F-box associated domain containing) [NCBI Gene 342897] {aka FBXO50, NCCRP-1}, PLG (plasminogen) [NCBI Gene 5340] {aka HAE4}, S100A8 (S100 calcium binding protein A8) [NCBI Gene 6279] {aka 60B8AG, CAGA, CFAG, CGLA, CP-10, L1Ag}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, C9 (complement C9) [NCBI Gene 735] {aka ARMD15, C9D}, CCL25 (C-C motif chemokine ligand 25) [NCBI Gene 6370] {aka Ck beta-15, Ckb15, SCYA25, TECK, TECKvar}, EEF2 (eukaryotic translation elongation factor 2) [NCBI Gene 1938] {aka EEF-2, EF-2, EF2, SCA26}, GP1BA (glycoprotein Ib platelet subunit alpha) [NCBI Gene 2811] {aka BDPLT1, BDPLT3, BSS, CD42B, CD42b-alpha, DBPLT3}, TUBA1B (tubulin alpha 1b) [NCBI Gene 10376] {aka K-ALPHA-1}, C3 (complement C3) [NCBI Gene 718] {aka AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1}, BLMH (bleomycin hydrolase) [NCBI Gene 642] {aka BH, BMH}, GC (GC vitamin D binding protein) [NCBI Gene 2638] {aka DBP, DBP-maf, DBP/GC, GRD3, Gc-MAF, GcMAF}, RBP4 (retinol binding protein 4) [NCBI Gene 5950] {aka MCOPCB10, RDCCAS}, CD244 (CD244 molecule) [NCBI Gene 51744] {aka 2B4, NAIL, NKR2B4, Nmrk, SLAMF4}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, ABO (ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase) [NCBI Gene 28] {aka A3GALNT, A3GALT1, GTA, GTB, NAGAT}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, PRDX3 (peroxiredoxin 3) [NCBI Gene 10935] {aka AOP-1, AOP1, HBC189, MER5, PPPCD, PRO1748}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, EPPK1 (epiplakin 1) [NCBI Gene 83481] {aka EPIPL, EPIPL1}
- **Diseases:** pulmonary injury (MESH:D055370), chronic kidney and liver disease (MESH:D051436), endothelial injury (MESH:D057772), DVT (MESH:D020246), antiphospholipid syndrome (MESH:D016736), Cancer (MESH:D009369), COVID infection (MESH:D000086382), endothelial dysfunction (MESH:D014652), atrial fibrillation (MESH:D001281), lung diseases (MESH:D008171), lung cancer (MESH:D008175), cardiovascular diseases (MESH:D002318), blood coagulation (MESH:D001778), acute myocardial infarction (MESH:D009203), acute cerebral venous sinus thrombosis (MESH:D012851), atherosclerosis (MESH:D050197), cardiac death (MESH:D003643), VTE (MESH:D054556), hypertension (MESH:D006973), influenza (MESH:D007251), thrombosis (MESH:D013927), platelet (MESH:D001791), Inflammation (MESH:D007249), alveolar injury (MESH:D014947), hypoxia (MESH:D000860), pulmonary hypertension (MESH:D006976), chronic pulmonary diseases (MESH:D002908), Hemolysis (MESH:D006461), NSCLC (MESH:D002289), EBC (MESH:C565384), Pulmonary Embolism (MESH:D011655), thrombophilia (MESH:D019851), thromboembolic (MESH:D013923), tricuspid regurgitation (MESH:D014262), hypoxic (MESH:D002534), Obese (MESH:D009765), congestive heart failure (MESH:D006333)
- **Chemicals:** urea (MESH:D014508), phosphotyrosine (MESH:D019000), antivitamin K (MESH:C011664), 3-phosphoinositide (-), ROS (MESH:D017382), retinol (MESH:D014801), Polystyrene (MESH:D011137)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Sus scrofa (pig, species) [taxon 9823], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]
- **Mutations:** G20210A, AUC of 0

## Full text

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## Figures

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## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12922095/full.md

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Source: https://tomesphere.com/paper/PMC12922095