ArticleArteriosclerosis, thrombosis, and vascular biology2023
Causal Role for Neutrophil Elastase in Thoracic Aortic Dissection in Mice.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- The Role of Cysteine-Rich Protein 2 in Aortic Dissection: Implications for VSMC Phenotypic Modulation-CSRP2 Impedes the Progression of Aortic Dissection.Biomolecules · 2026Article
- Endothelial GABA protects against aortic dissection by inhibiting endothelial and mitochondrial dysfunction and maintaining vascular homeostasis.Signal transduction and targeted therapy · 2026Article
- Revealing FPR1 as a potential pathogenic biomarker for aortic dissection based on Mendelian randomization, single-cell transcriptome and clinical data analysis.Biology direct · 2026Article
- Thrombo-inflammation as a missing variable in thoracic aortic intervention timing: toward a biology-informed threshold.Frontiers in cardiovascular medicine · 2026Review
- Vascular Smooth Muscle Cell Metabolic Disorders in the Occurrence and Development of Aortic Aneurysms and Dissections: Implications for Therapy.Biomedicines · 2025Review
- From inflammation to remodelling: A novel BASP1Journal of advanced research · 2025Article
- Calpain-2-Mediated Endothelial Focal Adhesion Disruption in Thoracic Aortic Dissection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Extracellular matrix in vascular homeostasis and disease.Nature reviews. Cardiology · 2025Review
- Calpain inhibition as a novel therapeutic strategy for aortic dissection with acute lower extremity ischemia.Molecular medicine (Cambridge, Mass.) · 2025Observational
- Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes.NPJ genomic medicine · 2025Article
- The innate immune axis drives aortic dissection pathogenesis through inflammation and presents novel therapeutic targets.Frontiers in immunology · 2025Review
- Integrative Bioinformatics Analysis to Identify Key Ferroptosis-Related Genes and Immune Infiltration in Aortic Aneurysm and Dissection: Implication of PTGS2.Journal of inflammation research · 2025Article
- Independent and Interactive Roles of Immunity and Metabolism in Aortic Dissection.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThoracic aortic dissection (TAD) is a life-threatening aortic disease without effective medical treatment. Increasing evidence has suggested a role for NE (neutrophil elastase) in vascular diseases. In this study, we aimed at investigating a causal role for NE in TAD and exploring the molecular mechanisms involved.
methodsβ-aminopropionitrile monofumarate was administrated in mice to induce TAD. NE deficiency mice, pharmacological inhibitor GW311616A, and adeno-associated virus-2-mediated in vivo gene transfer were applied to explore a causal role for NE and associated target gene in TAD formation. Multiple functional assays and biochemical analyses were conducted to unravel the underlying cellular and molecular mechanisms of NE in TAD.
resultsNE aortic gene expression and plasma activity was significantly increased during β-aminopropionitrile monofumarate-induced TAD and in patients with acute TAD. NE deficiency prevents β-aminopropionitrile monofumarate-induced TAD onset/development, and GW311616A administration ameliorated TAD formation/progression. Decreased levels of neutrophil extracellular traps, inflammatory cells, and MMP (matrix metalloproteinase)-2/9 were observed in NE-deficient mice. TBL1x (F-box-like/WD repeat-containing protein TBL1x) has been identified as a novel substrate and functional downstream target of NE in TAD. Loss-of-function studies revealed that NE mediated inflammatory cell transendothelial migration by modulating TBL1x-LTA4H (leukotriene A4 hydrolase) signaling and that NE regulated smooth muscle cell phenotype modulation under TAD pathological condition by regulating TBL1x-MECP2 (methyl CpG-binding protein 2) signal axis. Further mechanistic studies showed that TBL1x inhibition decreased the binding of TBL1x and HDAC3 (histone deacetylase 3) to
conclusionsWe unravel a critical role of NE and its target TBL1x in regulating inflammatory cell migration and smooth muscle cell phenotype modulation in the context of TAD. Our findings suggest that the NE-TBL1x signal axis represents a valuable therapeutic for treating high-risk TAD patients.
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