PIAS1 attenuates the progression of abdominal aortic aneurysm by stabilizing PPARγ through SUMOylation.

BACKGROUND AND PURPOSE: Protein inhibitor of activated STAT 1 (PIAS1) functions as a SUMO E3 ligase, regulating cardiovascular diseases by promoting the SUMOylation of target proteins; however, its role in abdominal aortic aneurysm (AAA) remains unclear. Currently, molecular targeted therapies for AAA are still very limited. This study aimed to clarify whether PIAS1 regulates the stability of the PPARγ protein through SUMOylation to elucidate its molecular mechanisms in AAA formation and to evaluate its potential as a novel therapeutic target.

METHODS

AAA rat models were established via the infusion of porcine pancreatic elastase, and an in vitro cell model was constructed by treating human umbilical vein endothelial cells (HUVECs) with Ang II. Flow cytometry, ELISA, H&E staining, and EVG staining were used to assess cell and abdominal aortic tissue damage, while RT-qPCR and Western blotting were used to detect the expression of relevant genes and proteins.

RESULTS

This study revealed that PIAS1 is expressed at low levels in AAA. The overexpression of PIAS1 effectively inhibited Ang II-induced lipid accumulation and inflammatory responses in HUVECs and AAA rats, alleviated pathological damage and apoptosis in the abdominal aorta, and alleviated the progression of AAA. With respect to the regulatory mechanism, the SUMOylation and expression levels of PPARγ are downregulated in AAA. PIAS1 primarily stabilizes PPARγ expression by promoting its SUMOylation, thereby inhibiting lipid accumulation and inflammatory responses. Further studies revealed that SENP3 is highly expressed in AAA and that PIAS1 can downregulate SENP3 levels, thereby attenuating its deSUMOylation effect on PPARγ and ultimately promoting the SUMOylation and expression of PPARγ.

CONCLUSION

PIAS1 alleviates the progression of AAA by inhibiting SENP3 expression, thereby promoting PPARγ SUMOylation and protein expression, which in turn reduces lipid accumulation and inflammatory responses.