ArticleClinical and translational medicine2024
CircHipk3 serves a dual role in macrophage pyroptosis by promoting NLRP3 transcription and inhibition of autophagy to induce abdominal aortic aneurysm formation.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- SERCA2 gatekeeper role in aortic autophagy: targeting the CaActa pharmacologica Sinica · 2026Article
- circGAB1 Activates Autophagy to Promote Sepsis-Associated Acute Kidney Injury by Interacting with ELAVL1 to Activate the HMGB3/β-catenin Signaling Pathway.Applied biochemistry and biotechnology · 2026Article
- Maresin 1 activates autophagy through SIRT1/PPAR-γ signaling to mitigate high glucose-induced pyroptosis in human retinal pigment epithelial cells.Experimental and therapeutic medicine · 2026Article
- Comprehensive analysis for the role of macrophage-driven genes in abdominal aortic aneurysm.Cardiovascular diagnosis and therapy · 2026Article
- PKM2 preconditioning protects endothelial cells from pyroptosis and BBB disruption via NRF2/TRX/TXNIP signaling in neonatal hypoxic-ischemic brain injury.Journal of neuroinflammation · 2026Article
- The primary cilium-autophagy axis in vascular homeostasis and cardiovascular disease: mechanistic crosstalk and evidence boundaries.Frontiers in cardiovascular medicine · 2026Review
- The role of macrophages in aortic physiology and pathophysiology.Frontiers in immunology · 2026Review
- CircHIPK3 promotes the progression of B-cell acute lymphoblastic leukemia in children by binding to STAT3.Frontiers in pharmacology · 2026Article
- Decoding the molecular mechanisms of pyroptosis and its therapeutic development prospects.Frontiers in cell and developmental biology · 2026Review
- Unveiling the Role of circRNAs in Pyroptotic Signalling: From Molecular Crosstalk to Disease Modulation.Journal of cellular and molecular medicine · 2025Review
- NLRP3 Inflammasome Activation in Liver Disorders: From Molecular Pathways to Therapeutic Strategies.Journal of inflammation research · 2025Review
- CircHipk3 serves a dual role in macrophage pyroptosis by promoting NLRP3 transcription and inhibition of autophagy to induce abdominal aortic aneurysm formation.Clinical and translational medicine · 2024Article
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Authors and funding
9 authors.
Funding
Abstract
aimsCircRNAs could regulate macrophage pyroptosis, which has the potential in promoting the synergistic effect of inflammation and matrix metalloproteinase (MMP) activity in abdominal aortic aneurysm (AAA). But the roles of circRNAs in modulating macrophage pyroptosis in the AAA remain unknown. This study explored the contribution to AAA of circHipk3, which was macrophage pyroptosis promoter, and the underlying mechanism. METHODS AND
resultsCircHipk3 was markedly upregulated in aortic aneurysms compared with that in normal arteries. In mice treated with circHipk3 contributed to macrophage pyroptosis, subsequently promoting the synergistic effect of inflammation and MMP synthesis, and significantly accelerated angiotensin (Ang) II- and porcine pancreatic elastase (PPE)-induced AAA formation. Mechanically, chromatin isolation by RNA purification (ChIRP) indicated that circHipk3 facilitated macrophage pyroptosis by interaction with Stat3, increase the NLRP3 level in the aorta, and by binding Snd1 to promote Ptbp1 mRNA degradation to inhibit autophagy. Therefore, our study revealed the important role of circHipk3 in macrophage pyroptosis and thus significantly improved the outcome of AAA.
conclusionsCircHipk3 serves a dual role in augmenting macrophage pyroptosis by interaction with Stat3, increase the NLRP3 level, and by binding Snd1 to promote Ptbp1 mRNA degradation to inhibit autophagy, thereby inducing aneurysm formation and progression. KEY POINTS: 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.
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