ALKBH5 Exacerbates Aortic Dissection by Promoting Inflammatory Response and Apoptosis of Aortic Smooth Muscle Cells via Regulating lnc-TMPO-AS1/EZH2/IRAK4 Signals in an m6A Modification Manner

Figure 2

ALKBH5 exacerbates AngII-induced inflammatory response and apoptosis of HASMCs and increases the incidence of AD in AngII-infused mice. (a, b) The interference effects of LV-ALKBH5 and sh-ALKBH5 on ALKBH5 expression in HASMCs were detected by qRT-PCR and western blot. (c–f) The overexpression of ALKBH5 evidently enhanced the promoting effect of AngII on the secretion of inflammatory cytokines in HASMCs. (g–j) ALKBH5 knockdown could suppress the expression of the genes corresponding to the aforesaid inflammatory factors in HASMCs. (k) The expression of pNFκB was upregulated in the AngII-treated group and ALKBH5 significantly enhanced the promoting effect of AngII on it. (l) AngII could induce HASMC apoptosis, and this effect was significantly enhanced when ALKBH5 was overexpressed and weakened when it is silenced. (m) AngII could significantly increase the incidence of AD, and this impact was significantly enhanced by the overexpression of ALKBH5 and reduced by its knockdown. (n) Mice in the AngII+LV-ALKBH5 group and AngII+sh-ALKBH5 group had the shortest and longest lifespans, respectively. (o, p) Gross observations showed that the aorta of AD mice was significantly congested and thickened, and histological observations confirmed the destruction of aortic tissue and the formation of AD. Data represented the from three independent experiments, versus the Ctrl group; ^# versus the AngII+ LV-NC/sh-NC group; ^ns versus the AngII group.

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