Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function

Pastorelli, Luca; Dozio, Elena; Pisani, Laura Francesca; Boscolo-Anzoletti, Massimo; Vianello, Elena; Munizio, Nadia; Spina, Luisa; Tontini, Gian Eugenio; Peyvandi, Flora; Romanelli, Massimiliano Marco Corsi; Vecchi, Maurizio

doi:10.1155/2015/189341

Cited by 24 publications

(23 citation statements)

References 45 publications

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“…Deficiency of protein C, protein S and antithrombin and factor V Leiden mutation and prothrombin 20210A gene variant are genetic risk factors for DVT [19]. In addition, diseases such as IBD [20], CKD [8], SLE [21] and cancer [22] are commonly associated with an increased risk for clot formation.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore conditions that increase bacterial translocation such as IBD have been implicated in the development of venous thrombosis through higher circulating levels of lipopolysaccharide (LPS) along with increased expression of Toll-like receptor 4 (TLR-4), an innate immune receptor responsible for LPS recognition [20]. TLR-4 is expressed by platelets and endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

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Association between small intestinal bacterial overgrowth and deep vein thrombosis

André

Fialho

Schenone

et al. 2016

Gastroenterol. Rep.

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Objective: Small intestinal bacterial overgrowth (SIBO) has been associated with several diseases. The association between SIBO and deep vein thrombosis (DVT) has not been investigated. This study was aimed to investigate the frequency and risk factors for the development of DVT in patients tested for SIBO.Methods: All 321 eligible patients were included from the Cleveland Clinic Gastrointestinal Motility Lab databank from January 2008 to January 2014. Patients who were evaluated with glucose hydrogen/methane breath test as well as Doppler ultrasonography for suspected DVT were included. Patients with catheter-related DVT were excluded. The primary outcomes were the frequency and risk factors (including SIBO) for DVT in this patient population.Results: Of the 321-case cohort, 144 patients (44.9%) tested positive for SIBO, and 53 (16.5%) had ultrasonographic findings of DVT. SIBO evaluation before the evaluation of DVT occurred in 201 patients (median time from the breath test to ultrasonography: 27 months; interquartile range [IQR]: 11.0–45.0 months), and SIBO evaluation after evaluation for DVT occurred in 120 patients (median time from ultrasonography to the breath test: 30 months; IQR: 11.8–54.3 months). In the univariate analysis, DVT was associated with family history of thromboembolic events (35.8% vs 16.0%, P=0.001), chronic kidney diseases (CKD; 26.4% vs 13.4%, P=0.019) and the presence of SIBO (69.8% vs 39.9%, P<0.001). In the multivariate analysis, family history of thromboembolic events (odds ratio [OR]: 3.39; 95% confidence interval [CI]: 1.67–6.87; P<0.001), CKD (OR: 2.23; 95%CI: 1.04–4.74; P = 0.037), and the presence of SIBO (OR: 3.27; 95% CI: 1.70–6.32; P < 0.001) remained independently associated with DVT.Conclusion: SIBO was found to be associated with DVT. The nature of this association warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association between small intestinal bacterial overgrowth and deep vein thrombosis

André

Fialho

Schenone

et al. 2016

Gastroenterol. Rep.

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“…Although the pathogenesis of IBD remains obscure, there is evidence that intestinal barrier dysfunction is the primary driver (Hindryckx and Laukens, 2012; Pastorelli et al, 2015). Tight junction dysfunction leads to damage of the intestinal barrier, which permits passage of diverse pathogens (Jin and Blikslager, 2016).…”

Section: Mclk In Ibdmentioning

confidence: 99%

Myosin Light Chain Kinase: A Potential Target for Treatment of Inflammatory Diseases

et al. 2017

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Myosin light chain kinase (MLCK) induces contraction of the perijunctional apical actomyosin ring in response to phosphorylation of the myosin light chain. Abnormal expression of MLCK has been observed in respiratory diseases, pancreatitis, cardiovascular diseases, cancer, and inflammatory bowel disease. The signaling pathways involved in MLCK activation and triggering of endothelial barrier dysfunction are discussed in this review. The pharmacological effects of regulating MLCK expression by inhibitors such as ML-9, ML-7, microbial products, naturally occurring products, and microRNAs are also discussed. The influence of MLCK in inflammatory diseases starts with endothelial barrier dysfunction. The effectiveness of anti-MLCK treatment may depend on alleviation of that primary pathological mechanism. This review summarizes evidence for the potential benefits of anti-MLCK agents in the treatment of inflammatory disease and the importance of avoiding treatment-related side effects, as MLCK is widely expressed in many different tissues.

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“…This raises the question as to which form dominates in CSF. In studies using identical ELISA kits, membrane forms of TLRs have been ignored in discussions about the origins of the assayed sTLR [ 3 , 4 , 13 , 14 ]. TLRs are abundantly expressed in CNS and their mRNA is upregulated in the brain in SAH and ischaemic models [ 15 – 17 ].…”

Section: Discussionmentioning

confidence: 99%

Soluble Toll-Like Receptors 2 and 4 in Cerebrospinal Fluid of Patients with Acute Hydrocephalus following Aneurysmal Subarachnoid Haemorrhage

et al. 2016

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BackgroundToll-like receptor (TLR) signalling begins early in subarachnoid haemorrhage (SAH), and plays a key role in inflammation following cerebral aneurysm rupture. Available studies suggest significance of endogenous first-line blockers of a TLR pathway—soluble TLR2 and 4.MethodsEighteen patients with SAH and acute hydrocephalus underwent endovascular coiling and ventriculostomy; sTLR2 and 4 levels were assayed in cerebrospinal fluid (CSF) collected on post-SAH days 0–3, 5, and 10–12. Release kinetics were defined. CSF levels of sTLR2 and 4 were compared with a control group and correlated with the clinical status on admission, the findings on imaging, the degree of systemic inflammation and the outcome following treatment.ResultsNone of study group showed detectable levels of sTLR2 and 4 on post-SAH day 0–3. 13 patients showed increased levels in subsequent samples. In five SAH patients sTLR2 and 4 levels remained undetectable; no distinctive features of this group were found. On post-SAH day 5 the strongest correlation was found between sTLR2 level and haemoglobin level on admission (cc = -0.498, P = 0.037). On post-SAH day 10–12 the strongest correlation was revealed between sTLR2 and treatment outcome (cc = -0.501, P = 0.076). Remaining correlations with treatment outcome, status at admission, imaging findings and inflammatory markers on post-SAH day 5 and 10–12 were negligible or low (-0.5 ≤ cc ≤ 0.5).ConclusionsIn the majority of cases, rupture of a cerebral aneurysm leads to delayed release of soluble TLR forms into CSF. sTLR2 and 4 seem to have minor role in human post-SAH inflammation due to delayed release kinetics and low levels of these protein.

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Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function

Cited by 24 publications

References 45 publications

Association between small intestinal bacterial overgrowth and deep vein thrombosis

Association between small intestinal bacterial overgrowth and deep vein thrombosis

Myosin Light Chain Kinase: A Potential Target for Treatment of Inflammatory Diseases

Soluble Toll-Like Receptors 2 and 4 in Cerebrospinal Fluid of Patients with Acute Hydrocephalus following Aneurysmal Subarachnoid Haemorrhage

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