Mucosa associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is not only an intracellular signaling scaffold protein but also a paracaspase that plays a key role in the signal transduction and cellular activation of lymphocytes and macrophages. However, its role in endothelial cells remains unknown. Here we report that pharmacological inhibition of MALT1 protease activity strongly suppresses endothelial activation via enhancing MCPIP1 expression. Treatment with MALT1 protease inhibitors selectively inhibited TNFα-induced VCAM-1 expression in HUVECs and LPS-induced VCAM-1 expression in mice. In addition, Inhibition of MALT1 protease activity also significantly inhibited TNFα-induced adhesion of THP-1 monocytic cells to HUVECs. To explore the mechanisms, MALT1 inhibitors does not affect the activation of NF-κB signaling pathway in HUVEC. However, they can stabilize MCPIP1 protein and significantly enhance MCPIP1 protein level in endothelial cells. These results suggest that MALT1 paracaspase also targets MCPIP1 and degrade MCPIP1 protein in endothelial cells similar as it does in immune cells. Taken together, the study suggest inhibition of MALT1 protease activity may represent a new strategy for prevention/therapy of vascular inflammatory diseases such as atherosclerosis.

粘膜相关淋巴组织淋巴瘤易位蛋白1（MALT1）不仅是一种细胞内信号转导支架蛋白，而且还是一种半胱天冬酶，其在淋巴细胞和巨噬细胞的信号转导和细胞活化中起关键作用。然而，其在内皮细胞中的作用仍然未知。在这里我们报告说，药理抑制MALT1蛋白酶的活性可以通过增强MCPIP1的表达强烈抑制内皮细胞的活化。用MALT1蛋白酶抑制剂处理可选择性抑制HUVEC中TNFα诱导的VCAM-1表达和小鼠LPS诱导的VCAM-1表达。另外，抑制MALT1蛋白酶活性也显着抑制了TNFα诱导的THP-1单核细胞与HUVEC的粘附。探索机制 MALT1抑制剂不影响HUVEC中NF-κB信号通路的激活。但是，它们可以稳定MCPIP1蛋白并显着提高内皮细胞中的MCPIP1蛋白水平。这些结果表明，MALT1对半胱天冬酶也靶向MCPIP1并降解内皮细胞中的MCPIP1蛋白，就像在免疫细胞中一样。综上所述，研究表明抑制MALT1蛋白酶的活性可能代表了预防/治疗血管炎性疾病（如动脉粥样硬化）的新策略。