TPI1 Contributes to the Development of Aortic Aneurysm by Promoting VSMC Phenotypic Switching and MMP2/9 Secreting

Abstract Background: Triosephosphate isomerase 1 (TPI1) is a crucial enzyme in glycolysis/gluconeogenesis and has been associated with a variety of diseases. However, there is little information on TPI1 and aortic aneurysms (AA). This study was designed to reveal the association between TPI1 and aortic aneurysms, and the mechanisms underlying TPI1 activity in AAs. Methods: Tandem Mass Tag (TMT)-based Liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) and the Mann-Whitney test were used to compare variables between AA and normal aortic tissues. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed using Fun-Rich software. The expression of the TPI1 protein in human aortic tissues was verified by Western blotting. A mouse AA model was established by infusing Ang-II for 4 weeks, then the expression of TPI1, SM22, α-SMA, OPN and MMP2/9 proteins were evaluated by western blotting. TPI1 overexpression was achieved by transfection of TPI mRNA, and its effect on gene expression was studied by RT-qPCR and western blotting, which included SM22, α-SMA, OPN, and MMP2/9. Ang II-induced expression of TPI1 and phenotypic-related genes in VSMCs. Results: TPI1 is closely related to the glycolysis/gluconeogenesis pathway and is higher in AA. Expression of TPI1 was upregulated in AA aortic samples of both human and mouse models, p < 0.05. Vascular smooth muscle cells (VSMCs) transfected with TPI mRNA induced lower mRNA and protein levels of SM22 and α-SMA, and higher levels of OPN, p < 0.05. Furthermore, the expression of MMP2/9 was also increased, P < 0.05. The same results that from the VSMCs were induced by Ang-II. Conclusions: Higher expression of TPI1 is associated with AA and contributes to the phenotypic switching of VSMC and increased expression of MMP2/9 observed in AA. TPI1 represents a novel target warranting further research towards improving treatment outcomes in candidates with AA.