Interleukin-6: A Potential Target for Post-Thrombotic Syndrome

Wojcik, Brandon M.; Wrobleski, Shirley K.; Hawley, Angela E.; Wakefield, Thomas W.; Myers, Daniel D.; Diaz, José A.

doi:10.1016/j.avsg.2010.09.003

Cited by 82 publications

(110 citation statements)

References 49 publications

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“…34 Several studies have shown that gal3 upregulates IL-6 in pathologic conditions. 7,8,35 We have previously shown that IL-6 plays a key role in promoting VT. 15 We therefore decided to investigate the relationship between gal3 and IL-6 during VT. The strong correlation we observed between gal3 and IL-6 expression in the vein wall led us to examine whether these were mechanistically involved in venous thrombogenesis.…”

Section: Gal3 Plays a Proinflammatory Role In The Context Of Vtmentioning

confidence: 99%

“…For histology, the IVC, aorta, and surrounding tissues were removed as previously described. 15 Isolation of PLTs, microparticles, and WBCs PLT, microparticle, and leukocyte isolation. See supplemental Methods, available on the Blood Web site.…”

Section: Inferior Vena Cava Stasis Modelmentioning

confidence: 99%

“…Wojcik et al showed that neutralizing IL-6 significantly reduces VT via reductions in CCL2. 15 Although gal3bp and gal3 have been shown to be important in a number of diseases, their role in VT has yet to be investigated.…”

Section: Introductionmentioning

confidence: 99%

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The role of galectin-3 and galectin-3–binding protein in venous thrombosis

DeRoo

Wrobleski

Shea

et al. 2015

Blood

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• We determined the location of gal3bp and gal3 and their role in promoting VT and leukocyte/endothelial cell interactions for the first time.• Gal3bp and gal3 have the potential to be used as targets for future VT therapies.Galectin-3-binding protein (gal3bp) and its receptor/ligand, galectin-3 (gal3), are secreted proteins that initiate signaling cascades in several diseases, and recent human proteomic data suggest they may play a role in venous thrombosis (VT). We hypothesized that gal3bp and gal3 may promote VT. Using a mouse stasis model of VT, we found that gal3bp and gal3 were localized on vein wall, red blood cells, platelets, and microparticles, whereas leukocytes expressed gal3 only. Gal3 was dramatically increased during early VT and gal3bp:gal3 colocalized in the leukocyte/endothelial cell interface, where leukocytes were partially attached to the vein wall. Thrombus size correlated with elevated gal3 and interleukin-6 (IL-6) vein wall levels. Recombinant gal3 promoted VT and increased vein wall IL-6 mRNA. Although recombinant gal3 restored the VT size in gal3 2/2 mice, it had no effect on IL6 2/2 mice, suggesting that gal3:gal3bp promotes VT through IL-6. Moreover, significantly fewer activated neutrophils were present in the gal3 2/2 vein walls. In a group of human patients, elevated circulating gal3bp correlated with acute VT. In conclusion, gal3bp:gal3 play a critical role in VT, likely via IL-6 and PMN-mediated thrombotic mechanisms, and may be a potential biomarker in human VT. (Blood. 2015;125(11):1813-1821

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Section: Gal3 Plays a Proinflammatory Role In The Context Of Vtmentioning

confidence: 99%

Section: Inferior Vena Cava Stasis Modelmentioning

confidence: 99%

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The role of galectin-3 and galectin-3–binding protein in venous thrombosis

DeRoo

Wrobleski

Shea

et al. 2015

Blood

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“…While these studies suggest that IL-6 may be used as a marker for VT, its role as an active cytokine in the development of PTS has been recently established. 45 Using the …”

Section: Interleukin-6mentioning

confidence: 99%

Inflammation and Acute Venous Thrombosis

Díaz¹

2011

Oncology &Amp; Hematology Review (US)

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Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE occurs worldwide, and in all age groups and socioeconomic populations in North America and western Europe.1,2 In a recent study by Heit et al., the estimated total annual cases of VTE occurring in the US exceeded 900,000, of which more than 250,000 were fatal. 3 Despite progress in medicine and biology, no changes in the incidence of VTE were noted during the 25-year cohort study. InflammationInflammation is a complex, highly regulated biological process that can be triggered by several stimuli, such as pathogens, noxious mechanical and chemical agents, and autoimmune responses. 10 In the clinical setting, inflammation is described as redness and swelling with heat and pain. Biologically, these signs and symptoms are explained by an increasing microvascular caliber, enhanced vascular permeability, leukocyte recruitment, and the release of inflammatory mediators. 10Inflammation in physiologic states is a controlled response that protects against further injury and clears damaged tissue. In disease states such as sepsis, however, uncontrolled inflammation can lead to a marked breakdown of the extracellular matrix as well as organ destruction. 10Inflammation can also be acute or chronic-two well-characterized states in which neutrophils and monocytes, respectively, play an important role. Similarly, DVT is a process with acute and chronic phases. In this setting, the main cells observed during acute DVT are the neutrophils.Monocytes are observed during the chronic phase. This parallel between inflammation and DVT is highly suggestive of a relationship. Inflammation and Vein Thrombosis Endothelial CellsECs play a pivotal role in venous thrombosis in healthy individuals. While arterial thrombosis requires EC disruption with collagen exposure (as Inflammation and Acute Venous ThrombosisJose Antonio Diaz, MD published material that assesses the relationship between inflammation and acute vein thrombosis. The article will focus on the role of endothelial cells, leukocytes, platelets, and microparticles in acute vein thrombosis and discuss the role of thrombin, P-selectin, platelet-activating factor, endothelin-1, and nitric oxide from the perspective of inflammation.

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“…For example, in 2010, the inflammatory cytokine interleukin‐6 was shown to play a direct role in venous fibrosis, demonstrating its potential as a therapeutic target to prevent post thrombotic syndrome 3. More recently, the role of galectin‐3 and galectin‐3 binding protein in venous thrombosis was identified by DeRoo et al.…”

mentioning

confidence: 99%