CircHipk3 serves a dual role in macrophage pyroptosis by promoting NLRP3 transcription and inhibition of autophagy to induce abdominal aortic aneurysm formation

CircHipk3 is significantly upregulated in abdominal aortic aneurysms (AAA) compared to normal arteries, contributing to macrophage pyroptosis. CircHipk3 promotes the synergistic effect of inflammation and matrix metalloproteinase (MMP) activity, accelerating Angiotensin II- and porcine pancreatic elastase-induced AAA formation in mice. Mechanistically, CircHipk3 interacts with Stat3 to elevate NLRP3 levels and binds Snd1 to promote Ptbp1 mRNA degradation, inhibiting autophagy. CircHipk3's dual role in enhancing NLRP3 inflammasome activation and inhibiting autophagy makes it a critical regulator in AAA development and rupture. Targeting CircHipk3 may offer a novel therapeutic strategy to prevent pyroptosis and AAA development, positioning it as a potential treatment target.