Inflammatory cytokines inhibit ADAMTS13 synthesis in hepatic stellate cells and endothelial cells

Von Willebrand factor, ADAMTS13 activity, TNF-α and their relationships in patients with chronic kidney disease

“…On the other hand, the plasma TNF-α concentrations in sepsis patients were higher than those in CKD patients (23). In the Cao et al study, the incubation concentrations of TNF-α in hepatic stellate and endothelial cells were considerably higher than the plasma concentration (15). This may explain why our results for the plasma TNF-α concentration differ from those at a cellular level.…”

“…Our study revealed that the TNF-α levels were positively correlated with the VWF:Ag levels in CKD patients, which is consistent with the findings of a previous study by Bolton et al (2) on the relationship between inflammatory cytokines and endothelial dysfunction in chronic renal failure patients, as well as the results of a study on Henoch-Schönlein purpura patients (22). We also found that the plasma TNF-α levels were not correlated with ADAMTS13 activity in CKD patients, although certain studies have indicated that TNF-α inhibits ADAMTS13 synthesis without affecting VWF secretion in hepatic stellate and endothelial cells (15). On the one hand, in the above-mentioned study, the incubation of TNF-α with purified ADAMTS13 did not inhibit the proteolytic cleavage of VWF in vitro.…”

“…In a cell-based study, TNF-α was found to be involved in the synthesis, release and cleavage of VWF and ADAMTS13 in cultured hepatic stellate and endothelial cells (15). However, the relationship among these factors in CKD has yet to be investigated.…”

Decreased activity of plasma ADAMTS13 are related to enhanced cytokinemia and endotoxemia in patients with acute liver failure

“…Plasma IL-6 and IL-8 levels were significantly higher in patients with UL-VWFM than in those without it. It has been demonstrated in vitro with human umbilical vein endothelial cells that IL-6 inhibits the ADAMTS13 actions under flow conditions, while IL-8 stimulates UL-VWFM release (12).…”

“…Endotoxemia, due to Kupffer cell dysfunction and increased intestinal permeability, triggers pro-inflammatory cytokine production, possibly causing a systemic inflammatory response syndrome and microcirculatory disturbances, leading to MOF (10,11) Recent in vitro studies demonstrated associations of inflammatory cytokines with decreased ADAMTS13 activity (ADAMTS13:AC) (12) and increased UL-VWFM release from endothelial cells (13). Inflammation-associated ADAMTS13 deficiency promotes UL-VWFM formation in patients with sepsis (14), indicating a close linkage between cytokinemia, endotoxemia and ADAMTS13:AC in ALF.…”