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. 2021 Feb 5;12:631256. doi: 10.3389/fphar.2021.631256

FIGURE 2.

FIGURE 2

The mechanism of pyroptosis affecting endothelial cells in ALI. In ECs, caspase-1 not only induces pyroptosis, but also participates in the regulation of apoptosis. LPS and hemorrhagic shock (HS) are two major triggers for activation of caspase-1. TLR4 on the cell membrane recognizes LPS and up-regulates NLRP3 expression, thus inducing caspase-1-mediated pyroptosis. Besides, HS promotes the formation of inflammasomes via HMGB1/RAGE signaling pathway. Cleaved caspase-1 is responsible for the downstream caspase-9 and 3 activation leading to apoptosis in EC when Hcy and LPS stimulate simultaneously. Meanwhile, non-canonical pyroptosis pathway mediated by caspase-4/5/11 also occupies a certain role in endothelial pyroptosis. GSDMD cleaved by caspase-11 has another function that promotes mtDNA releases. Through cGAS/STING axis, mtDNA inhibits the expression of YAP, resulting in endothelial cell proliferation disorders. In addition to the above, the effect of pyroptosis on the pulmonary endothelial barrier still needs to be studied.