PLN inhibits vascular smooth muscle cell pyroptosis in abdominal aortic aneurysm via NF-κB/NLRP3 pathway

It's reported that PLN may exert a prominent function in the pathogenesis of abdominal aortic aneurysm (AAA). However, the effect of PLN on AAA is unclear. Thus, this study was executed to explore the role of PLN in AAA, as well as the involved potential molecular mechanism. Expression of PLN in AAA was confirmed in cell and mouse AAA models, and the effect of PLN on cell proliferation of Ang Ⅱ-induced HASMCs was investigated. Additionally, the levels of pyroptosis and NF-κB/NLRP3 pathway-related markers were evaluated after PLN overexpression in vivo and in vitro. Furthermore, IL-1β (NF-κB nuclear translocation activator) was employed to research the role of PLN in NF-κB activation. Both qRT-PCR, western blot and IHC validated the lower PLN expression in Ang Ⅱ-induced AAA mouse models, and mainly expressed in the smooth muscle cells (SMCs) of the tunica media of vascular vessels. In addition, pyroptosis, particularly VSMCs pyroptosis, occurred in abdominal aortic. PLN overexpression could significantly facilitate the cell vitality of Ang Ⅱ-treated HASMC cells. LDH level, and the protein expression levels of pro-Caspase1, Caspase1-p10, GSDMD-N, ASC, NLRP3, IL-1β, and IL-18 in Ang Ⅱ-induced HASMC cells were remarkedly reduced after PLN upregulation, as well as p-NF-κB-p65/NF-κB-p65 level. Similar results were also found in in vivo experiments. However, IL-1β administration could promote the PLN-decressed nuclear translocation of NF-κB and the levels of NLRP3, LDH in Ang Ⅱ-treated HASMCs. PLN is downregulated in AAA, and PLN inhibits VSMCs pyroptosis in AAA via NF-κB/NLRP3 pathway.