ArticleJCI insight2024
PI3Kγ promotes neutrophil extracellular trap formation by noncanonical pyroptosis in abdominal aortic aneurysm.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Neutrophil extracellular traps in cardiovascular disease: Mechanisms and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- Direct visualization of native GSDMD pores reveals lipid-driven stabilization during pyroptosis.Science advances · 2026Article
- Targeting pyroptosis to treat aortic aneurysms: From mechanism to drug discovery (Review).International journal of molecular medicine · 2026Review
- Neutrophils and Neutrophil Extracellular Traps in Hepatic Ischemia-Reperfusion Injury: Molecular Mechanisms and Therapeutic Strategies.International journal of molecular sciences · 2026Review
- The role of neutrophils in the pathogenesis of abdominal aortic aneurysms.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- PDK4 drives abdominal aortic aneurysm by promoting smooth muscle cell metabolic reprogramming and NLRP3-mediated pyroptosis.Nature communications · 2026Article
- Article
- Neutrophil extracellular traps and pyroptosis: a molecular nexus linking systemic autoimmune diseases to atherosclerosis.Frontiers in immunology · 2026Review
- Abdominal Aortic Aneurysm Pathomechanics, Current Understanding and Emerging Directions: A Perspective for 2025 and Beyond.Advances in experimental medicine and biology · 2026Review
- Identification and validation of hub genes related to neutrophil extracellular traps-mediated cell damage and immune recruitment during abdominal aortic aneurysm.Scientific reports · 2025Article
- NETosis and pyroptosis of immune cells in sepsis.Journal of translational internal medicine · 2025Article
- Irisin regulates integrin αvβ5/FAK/ERK to inhibit neutrophil extracellular traps formation and reduce pancreatic beta-cells pyroptosis in type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2025Article
- Targeting PI3Kγ in cancer.Trends in cancer · 2025Review
- Autophagy-mediated regulation of neutrophil inflammatory responses and its relevance to central nervous system diseases.Frontiers in aging neuroscience · 2025Review
- Therapeutic Targeting of Signaling Pathways in Abdominal Aortic Aneurysm: From Pathogenesis to Precision Medicine.Drug design, development and therapy · 2025Review
- Neutrophil extracellular traps: emerging drivers and therapeutic targets in abdominal aortic aneurysm pathogenesis.Experimental biology and medicine (Maywood, N.J.) · 2025Review
- Exploring the Spectrum of Long Non-Coding RNA CARMN in Physiological and Pathological Contexts.Biomolecules · 2024Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abdominal aortic aneurysm (AAA) is one of the most life-threatening cardiovascular diseases; however, effective drug treatments are still lacking. The formation of neutrophil extracellular traps (NETs) has been shown to be a crucial trigger of AAA, and identifying upstream regulatory targets is thus key to discovering therapeutic agents for AAA. We revealed that phosphoinositide-3-kinase γ (PI3Kγ) acted as an upstream regulatory molecule and that PI3Kγ inhibition reduced NET formation and aortic wall inflammation, thereby markedly ameliorating AAA. However, the mechanism of NET formation regulated by PI3Kγ remains unclear. In this study, we showed that PI3Kγ deficiency inactivated the noncanonical pyroptosis pathway, which suppressed downstream NET formation. In addition, PI3Kγ regulation of noncanonical pyroptosis was dependent on cyclic AMP/protein kinase A signaling. These results clarify the molecular mechanism and crosstalk between PI3Kγ and NETosis in the development of AAA, potentially facilitating the discovery of therapeutic options for AAA.
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