The third most prevalent cause of cardiovascular death is deep vein thrombosis (DVT). According to a number of studies, DVT develops when the inflammasome is activated, and the cytokine interleukin-1β (IL-1β) is secreted under conditions of limited venous flow. Inflammatory signaling initiated by IL-1 and other inflammatory mediators in endothelial cells is propagated by a signaling adaptor protein called Gab2, also known as Grb2-associated binder 2.

For a study, researchers demonstrated that Gab2 promotes the formation of the CBM signalosome, which mediates the activation of Rho and NF-B in endothelial cells, by facilitating the assembly of CARMA3 (CARD recruited membrane-associated guanylate kinase protein 3), BCL-10 (B-cell lymphoma 10), and MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1). IL-1-induced Rho-dependent exocytosis of P-selectin and von Willebrand factor (VWF) and the subsequent adhesion of neutrophils to endothelial cells were markedly diminished by gene silencing of Gab2 or MALT1, the effector signaling molecule in the CBM signalosome, or by pharmacological inhibition of MALT1 with a specific inhibitor, mepazine.

The expression of tissue factor and vascular cell adhesion molecule 1 that is triggered by IL-1 and NF-B was decreased as a result of MALT1 suppression. Gab2 loss or pharmacological inhibition of MALT1 decreased venous thrombosis brought on by inferior vena cava ligation-induced stenosis or stasis and inhibited the concentration of monocytes and neutrophils at the injury site, consistent with the in vitro observations.

Overall, the findings showed that the Gab2-MALT1 axis played a crucial but hitherto undetected function in thromboinflammation. The findings also pointed to an underappreciated function of the Gab2-MALT1 axis in thromboinflammation. MALT1 inhibitors that target the Gab2-MALT1 axis may prove to be an efficient way to treat DVT since they reduce thromboinflammation without causing bleeding issues.