Aim To explore the impact and mechanism of proprotein convertase subtilisin kexin 9 (PCSK9) on the progression of abdominal aortic aneurysm (AAA). Methods 6～8 week old ApoE－/－ mice were selected to establish the AAA model. AngiotensinⅡ (AngⅡ) was continuously infused through subcutaneous implantation of a micro-osmotic pump. The mice were fed with high-fat diet and killed after 28 days. The expression of PCSK9 in abdominal aortic smooth muscle cells was detected by immunohistochemistry and immunofluorescence in normal abdominal aortic blood vessels and AAA samples in human and mice. Primary cultured murine vascular smooth muscle cells (mVSMC) of C57BL/6 mice were treated with different concentrations of AngⅡ for 24 h, and the expression of PCSK9 mRNA and protein was detected. PCSK9 overexpression and knockdown cell models were established, and mitochondrial reactive oxygen species (mtROS), mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (MPTP) opening, and Z-DNA binding protein 1 (ZBP1) protein expression were detected. Bioinformatics was used to analyze the differential expression of multiple single-cell sequencing datasets to obtain the key differentially expressed genes, and to study their expression and role in AAA. Results Immunohistochemistry and immunofluorescence results showed that PCSK9 expression in human and mouse AAA increased (P＜0.01), and co-localized with smooth muscle. AngⅡpromoted PCSK9 expression in mVSMC in a concentration-dependent manner, the 2.0 μmol/L AngⅡ group showed a 2.9-fold and 1.1-fold increase in the expression of PCSK9 mRNA and protein, respectively (P＜0.01), with the most significant effect observed. After successfully constructing PCSK9 overexpression and PCSK9 interference mVSMC models, PCSK9 overexpression led to an increase in intracellular mtROS, a decrease in MMP, an increase in MPTP opening, and a decrease in cellular activity (P＜0.01); PCSK9 knockdown could reduce AngⅡinduced increase in mtROS, decrease in MMP and MPTP opening; compared with the siNC＋AngⅡgroup, the siPCSK9＋AngⅡ group showed a decrease in mtROS and an increase in the fluorescence brightness of MMP and MPTP (P＜0.05). Bioinformatics analysis revealed that ZBP1 was a core differentially expressed gene in AAA. Immunohistochemistry and immunofluorescence results showed that ZBP1 expression in human and mouse AAA tissues increased, and co-localized with smooth muscle. Western blot results showed that PCSK9 overexpression or treatment with 2.0 μmol/L AngⅡ could increase ZBP1 protein expression (P＜0.01), while PCSK9 knockdown could alleviate the increased ZBP1 expression caused by AngⅡ (P＜0.05). Conclusion PCSK9 may induce mitochondrial damage in smooth muscle cells, activate downstream molecule ZBP1 to cause cell damage, and promote the development of AAA.