Tissue factor coagulation pathway and blood cells activation state in renal insufficiency

Mercier, Éric; Branger, B.; Vécina, F.; Al-Sabadani, Bachir; Berlan, Jacques; Dauzat, M.; Fourcade, J; Gris, Jean‐Christophe

doi:10.1038/sj.thj.6200072

Cited by 39 publications

(33 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In support of our in vitro studies, renal insufficiency was associated with activation of the TF coagulation pathway and endothelial injury in end-stage disease aggravated by the HD treatment (17,31,37). A significant linear correlation between the PMNL priming index and TF expression in HUVEC exposed to PMNL suggests that the procoagulant state of HUVEC depends directly on the PMNL priming state.…”

Section: Discussionmentioning

confidence: 49%

Priming of polymorphonuclear leukocytes: a culprit in the initiation of endothelial cell injury

Jacobi¹,

Sela²,

Cohen³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Peripheral polymorphonuclear leukocytes (PMNL) in hemodialysis (HD) patients are primed, continually releasing and exposing the vascular endothelium to soluble factors such as reactive oxygen species and inflammatory mediators. To mimic the close proximity between PMNL and the endothelial monolayer and to monitor and characterize the influence of soluble mediators released from PMNL, we developed a novel cocultivation system using primary human umbilical vein endothelial cell (HUVEC) cultures and PMNL, with a sieve separating the two cell types to prevent direct adhesive effects. PMNL (10 6 ) from HD patients or from healthy normal controls were cocultivated with HUVEC (10 5 ) for 15 min, and endothelial cell injury was assessed by HUVEC morphology, cell detachment, and apoptosis. Proinflammatory changes were estimated by expression of HUVEC adhesion molecule P-selectin and by endothelial IL-8 and endothelial nitric oxide synthase mRNA. The levels of intracellular tissue factor reflected the procoagulant state, whereas NADPH oxidase activity served as an indicator for prooxidative changes in HUVEC. Mediators released from the primed PMNL triggered activation/dysfunction of endothelial cells, causing 1) an increase in endothelial cell detachment and apoptosis, 2) a proinflammatory state manifested by increased IL-8 mRNA expression and P-selectin on the endothelial surface, 3) activation of endothelial NADPH oxidase, 4) an increase in endothelial cell tissue factor that directly correlated with PMNL priming index, and 5) a decrease in endothelial nitric oxide synthase mRNA. Our data support a pathogenic link between PMNL priming and endothelial dysfunction, suggesting that PMNL priming is a potential new nontraditional risk factor for the development of atherosclerosis. cocultivation; nicotinamide adenine dinucleotide phosphate oxidase; polymorphonuclear leukocyte priming index

show abstract

Section: Discussionmentioning

confidence: 49%

Priming of polymorphonuclear leukocytes: a culprit in the initiation of endothelial cell injury

Jacobi¹,

Sela²,

Cohen³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Gondouin et al 40 showed the ability of IS and indole acetic acid to induce TF production through the aryl hydrocarbon receptor pathway, which was associated with increased procoagulant activity. CKD patients have elevated levels of soluble TF 41 and kynurenin, which like IS, belongs to the large group of the indoles and is associated with increased soluble TF levels and hypercoagulability in CKD patients. 42 Furthermore, endothelial microparticles, considered as markers of endothelial dysfunction, are shed on endothelial activation and involved in the regulation of coagulation by activating the TF pathway, 43 whereas both IS and pCS have been shown to elicit endothelial microparticle release in vitro.…”

Section: Discussionmentioning

confidence: 99%

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Pletinck

Glorieux

Schepers

et al. 2013

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.

show abstract

“…Recent clinical studies indicate that thrombosis occurs in the area of arterial stenosis caused by atherosclerotic incidents [5].…”

Section: Introductionmentioning

confidence: 99%

The influence of atherosclerosis and plasma D-dimer concentration in patients with a functioning arteriovenous fistula for maintenance hemodialysis

et al. 2008

View full text Add to dashboard Cite

show abstract

Tissue factor coagulation pathway and blood cells activation state in renal insufficiency

Cited by 39 publications

References 0 publications

Priming of polymorphonuclear leukocytes: a culprit in the initiation of endothelial cell injury

Priming of polymorphonuclear leukocytes: a culprit in the initiation of endothelial cell injury

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

The influence of atherosclerosis and plasma D-dimer concentration in patients with a functioning arteriovenous fistula for maintenance hemodialysis

Contact Info

Product

Resources

About