Low-Grade Activation of the Extrinsic Coagulation Pathway in Patients with Ulcerative Colitis.
Exosomes
Microparticles
Stromal cells
Thrombosis
Tissue factor
Ulcerative colitis
Journal
Digestive diseases and sciences
ISSN: 1573-2568
Titre abrégé: Dig Dis Sci
Pays: United States
ID NLM: 7902782
Informations de publication
Date de publication:
25 Sep 2024
25 Sep 2024
Historique:
received:
04
05
2024
accepted:
06
09
2024
medline:
26
9
2024
pubmed:
26
9
2024
entrez:
25
9
2024
Statut:
aheadofprint
Résumé
Ulcerative colitis (UC) increases the risk for venous thromboembolism. Tissue factor (TF) initiates the extrinsic coagulation pathway (ECP). To investigate the correlation of UC severity with latent ECP activation and TF expression in primary colonic stromal cells (PCSC). In plasma of 38 UC patients (31 males, disease duration 151 ± 25 months) and 28 healthy controls, exosomes and microparticles (EM) were counted. Moreover, TF protein concentration, activities of EM-bound TF (EM-TFa) and coagulation factor VII (FVIIa) were assessed. In PCSC in culture, TF mRNA (F3) from 12 patients with active UC and 7 controls was evaluated. UC patients had 4- and 3.7- times more exosomes and microparticles, respectively, than controls. TF protein in UC was correlated with several disease severity indices, such as partial Mayo score (pMs; r 0.443), albumin (- 0.362), ESR (0.353), PLT (0.575), and endoscopic Ms (eMs 0.468). EM-TFa was also significantly higher in UC and was correlated to SIBDQ (- 0.64), albumin (- 0.624), disease extent and eMs (0.422). Refractory-to-treatment patients had significantly higher TF protein, EM-TFa and FVIIa. Even within responders, the need for steroids or biologics correlated with a 2.2-times higher EM-TFa. PCSC from active UC maintained higher F3 than controls, which was correlated to pMs (0.56), albumin (- 0.543) and eMs. Treatment with cytokines further upregulated F3. P for all comparisons was < 0.05. Low-grade activation of the ECP associates with clinical, endoscopic UC activity and response to treatment. TF in PCSC mirrors its systemic activity and points to them as a source.
Sections du résumé
BACKGROUND
BACKGROUND
Ulcerative colitis (UC) increases the risk for venous thromboembolism. Tissue factor (TF) initiates the extrinsic coagulation pathway (ECP).
AIMS
OBJECTIVE
To investigate the correlation of UC severity with latent ECP activation and TF expression in primary colonic stromal cells (PCSC).
METHODS
METHODS
In plasma of 38 UC patients (31 males, disease duration 151 ± 25 months) and 28 healthy controls, exosomes and microparticles (EM) were counted. Moreover, TF protein concentration, activities of EM-bound TF (EM-TFa) and coagulation factor VII (FVIIa) were assessed. In PCSC in culture, TF mRNA (F3) from 12 patients with active UC and 7 controls was evaluated.
RESULTS
RESULTS
UC patients had 4- and 3.7- times more exosomes and microparticles, respectively, than controls. TF protein in UC was correlated with several disease severity indices, such as partial Mayo score (pMs; r 0.443), albumin (- 0.362), ESR (0.353), PLT (0.575), and endoscopic Ms (eMs 0.468). EM-TFa was also significantly higher in UC and was correlated to SIBDQ (- 0.64), albumin (- 0.624), disease extent and eMs (0.422). Refractory-to-treatment patients had significantly higher TF protein, EM-TFa and FVIIa. Even within responders, the need for steroids or biologics correlated with a 2.2-times higher EM-TFa. PCSC from active UC maintained higher F3 than controls, which was correlated to pMs (0.56), albumin (- 0.543) and eMs. Treatment with cytokines further upregulated F3. P for all comparisons was < 0.05.
CONCLUSION
CONCLUSIONS
Low-grade activation of the ECP associates with clinical, endoscopic UC activity and response to treatment. TF in PCSC mirrors its systemic activity and points to them as a source.
Identifiants
pubmed: 39322807
doi: 10.1007/s10620-024-08640-1
pii: 10.1007/s10620-024-08640-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Pfizer Inc.
ID : 64132481
Organisme : Greek Group for the Study of Inflammatory Bowel Disease
ID : 2018
Organisme : Greek Group for the Study of Inflammatory Bowel Disease
ID : 2018
Organisme : Greek Group for the Study of Inflammatory Bowel Disease
ID : 2018
Organisme : Greek Group for the Study of Inflammatory Bowel Disease
ID : 2018
Organisme : Greek Group for the Study of Inflammatory Bowel Disease
ID : 2018
Organisme : Greek Group for the Study of Inflammatory Bowel Disease
ID : 2018
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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