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- W4288052606 abstract "Abstract Deep vein thrombosis (DVT) is the third most common cause of cardiovascular mortality. Several studies suggest that DVT occurs at the intersection of dysregulated inflammation and coagulation upon activation of inflammasome and secretion of interleukin 1β (IL-1β) in restricted venous flow conditions. Our recent studies showed a signaling adapter protein, Gab2 (Grb2-associated binder 2), plays a crucial role in propagating inflammatory signaling triggered by IL-1β and other inflammatory mediators in endothelial cells. The present study shows that Gab2 facilitates the assembly of the CBM (CARMA3 [CARD recruited membrane-associated guanylate kinase protein 3]–BCL-10 [B-cell lymphoma 10]–MALT1 [mucosa-associated lymphoid tissue lymphoma translocation protein 1]) signalosome, which mediates the activation of Rho and NF-κB in endothelial cells. Gene silencing of Gab2 or MALT1, the effector signaling molecule in the CBM signalosome, or pharmacological inhibition of MALT1 with a specific inhibitor, mepazine, significantly reduced IL-1β–induced Rho-dependent exocytosis of P-selectin and von Willebrand factor (VWF) and the subsequent adhesion of neutrophils to endothelial cells. MALT1 inhibition also reduced IL-1β–induced NF-κB–dependent expression of tissue factor and vascular cell adhesion molecule 1. Consistent with the in vitro data, Gab2 deficiency or pharmacological inhibition of MALT1 suppressed the accumulation of monocytes and neutrophils at the injury site and attenuated venous thrombosis induced by the inferior vena cava ligation-induced stenosis or stasis in mice. Overall, our data reveal a previously unrecognized role of the Gab2–MALT1 axis in thromboinflammation. Targeting the Gab2–MALT1 axis with MALT1 inhibitors may become an effective strategy to treat DVT by suppressing thromboinflammation without inducing bleeding complications." @default.
- W4288052606 created "2022-07-28" @default.
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- W4288052606 date "2022-09-29" @default.
- W4288052606 modified "2023-10-14" @default.
- W4288052606 title "The Gab2–MALT1 axis regulates thromboinflammation and deep vein thrombosis" @default.
- W4288052606 cites W1600472471 @default.
- W4288052606 cites W1665357608 @default.
- W4288052606 cites W1963494914 @default.
- W4288052606 cites W1971827171 @default.
- W4288052606 cites W1977394930 @default.
- W4288052606 cites W1985372425 @default.
- W4288052606 cites W1987451876 @default.
- W4288052606 cites W1990720057 @default.
- W4288052606 cites W1994749414 @default.
- W4288052606 cites W2002920137 @default.
- W4288052606 cites W2014293477 @default.
- W4288052606 cites W2017141883 @default.
- W4288052606 cites W2023634900 @default.
- W4288052606 cites W2029473544 @default.
- W4288052606 cites W2034257077 @default.
- W4288052606 cites W2044368898 @default.
- W4288052606 cites W2045220907 @default.
- W4288052606 cites W2052034057 @default.
- W4288052606 cites W2062900990 @default.
- W4288052606 cites W2064558057 @default.
- W4288052606 cites W2074362469 @default.
- W4288052606 cites W2078817520 @default.
- W4288052606 cites W2080458188 @default.
- W4288052606 cites W2088417966 @default.
- W4288052606 cites W2088800018 @default.
- W4288052606 cites W2088852852 @default.
- W4288052606 cites W2093456571 @default.
- W4288052606 cites W2094424549 @default.
- W4288052606 cites W2104680298 @default.
- W4288052606 cites W2107054454 @default.
- W4288052606 cites W2108373994 @default.
- W4288052606 cites W2111419867 @default.
- W4288052606 cites W2119129191 @default.
- W4288052606 cites W2123789360 @default.
- W4288052606 cites W2124216243 @default.
- W4288052606 cites W2132822330 @default.
- W4288052606 cites W2137976684 @default.
- W4288052606 cites W2139372097 @default.
- W4288052606 cites W2145250151 @default.
- W4288052606 cites W2152502508 @default.
- W4288052606 cites W2153452283 @default.
- W4288052606 cites W2154649516 @default.
- W4288052606 cites W2162014238 @default.
- W4288052606 cites W2166456614 @default.
- W4288052606 cites W2172189015 @default.
- W4288052606 cites W2172191543 @default.
- W4288052606 cites W2257747161 @default.
- W4288052606 cites W2329051861 @default.
- W4288052606 cites W2368973723 @default.
- W4288052606 cites W2465426327 @default.
- W4288052606 cites W2525602907 @default.
- W4288052606 cites W2578853149 @default.
- W4288052606 cites W2605773822 @default.
- W4288052606 cites W2622667479 @default.
- W4288052606 cites W2762298725 @default.
- W4288052606 cites W2799522017 @default.
- W4288052606 cites W2803403137 @default.
- W4288052606 cites W2803984274 @default.
- W4288052606 cites W2880218695 @default.
- W4288052606 cites W2887281195 @default.
- W4288052606 cites W2889306620 @default.
- W4288052606 cites W2901928825 @default.
- W4288052606 cites W2936366881 @default.
- W4288052606 cites W2940777718 @default.
- W4288052606 cites W2943342045 @default.
- W4288052606 cites W2963080746 @default.
- W4288052606 cites W3046035988 @default.
- W4288052606 cites W3130001142 @default.
- W4288052606 cites W3140482925 @default.
- W4288052606 cites W3159729619 @default.
- W4288052606 cites W3174715604 @default.
- W4288052606 cites W3182944456 @default.
- W4288052606 cites W3189636447 @default.
- W4288052606 cites W3203536170 @default.
- W4288052606 cites W4205928507 @default.
- W4288052606 cites W4210725107 @default.
- W4288052606 doi "https://doi.org/10.1182/blood.2022016424" @default.
- W4288052606 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35895897" @default.
- W4288052606 hasPublicationYear "2022" @default.
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