Platelet-derived microparticles stimulated by anti-β2GPI/β2GPI complexes induce pyroptosis of endothelial cells in antiphospholipid syndrome
Platelet-derived microparticles stimulated by anti-β2GPI/β2GPI complexes induce pyroptosis of endothelial cells in antiphospholipid syndrome
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DOI：
10.1080/09537104.2022.2156492
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发表时间：
2023-12-31
期刊：
影响因子：
3.3
通讯作者：
Liu，Yanhong
中科院分区：
文献类型：
--
作者：
Di，Longjiang;Zha，Caijun;Liu，Yanhong
血小板微粒（PMPs）是由血小板释放到细胞外空间的囊泡，在抗磷脂抗体综合征中发挥作用。PMPs最近被认为是一种新的活细胞。越来越多的证据表明抗β 2糖蛋白（GPI）/β 2GPI复合物与PMPs的异常激活有关。尽管研究表明PMPs的异常激活可能导致内皮细胞的炎性坏死，但其潜在机制尚不清楚。我们发现，尽管PMPs数量的差异在统计学上不显著，但在抗β 2GPI/β 2GPI复合物的刺激期间，PMPs内的NLR家族pyrin结构域3（NLRP 3）增加。此外，我们证明了抗β 2GPI/β 2GPI复合物诱导的PMPs通过NLRP 3/核因子（NF）-kB/gasdermin D（GSDMD）信号通路以及NLRP 3/Caspase-1信号通路有效地刺激内皮细胞焦亡。此外，抑制PMP中的NLRP 3表达有效地降低了内皮细胞中的炎症反应和焦亡。我们的数据表明，由抗β 2 GPI/β 2 GPI复合物异常激活的PMPs在内皮细胞焦亡中起着至关重要的作用，这些研究为抗磷脂抗体综合征治疗过程中血栓形成的机制提供了重要的见解。
Platelet microparticles (PMPs) are vesicles that are released by platelets into the extracellular space and play a role in antiphospholipid antibody syndromes. PMPs have recently been recognized as a new and viable cell. There is growing evidence that the anti-ß2glycoprotein (GPI)/ß2GPI complex is associated with aberrant activation of PMPs. Although studies suggest that aberrant activation of PMPs may lead to inflammatory necrosis of endothelial cells, the underlying mechanisms remain unclear. We found that although the difference in the number of PMPs was not statistically significant, NLR family pyrin domain containing 3 (NLRP3) within PMPs was increased during stimulation of anti-ß2GPI/ß2GPI complexes. Furthermore, we demonstrated that anti-ß2GPI/ß2GPI complex-induced PMPs effectively stimulated endothelial cell pyroptosis via the NLRP3/nuclear factor (NF)-kB/gasdermin D (GSDMD) signaling pathway as well as the NLRP3/Caspase-1 signaling pathway. Additionally, inhibition of NLRP3 expression in PMPs effectively reduced the inflammatory response and pyroptosis in endothelial cells. Our data suggest that PMPs aberrantly activated by anti-ß2GPI/ß2GPI complexes play a vital role in endothelial cell pyroptosis, and these studies provide major insights into the mechanisms of thrombosis during the treatment of antiphospholipid antibody syndrome.