ArticleEBioMedicine2019
Macrophage metabolic reprogramming aggravates aortic dissection through the HIF1α-ADAM17 pathway
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 131 citations in OpenAlex.
- [Effects of exosomes derived from normoxic or hypoxic human umbilical vein endothelial cells on hypoxia-induced cardiomyocyte injury and cardiac fibroblast activationNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Reactive oxygen species in thoracic aortic dissection: Insights into mechanisms and disease progression.Redox biology · 2026Review
- Integrated Single-Cell and Spatial Analysis Reveals a Metabolic-Immune Axis Driving Aortic Dissection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial progenitor cells are associated with improved vascular repair in experimental aortic dissection.Scientific reports · 2026Article
- The role and therapeutic potential of succinate and succinylation in cardiovascular diseases.Clinical epigenetics · 2026Review
- Article
- IL-17RA signaling promotes the dedifferentiation of Paneth progenitors through ADAM17 to regenerate gut epithelium post-irradiation.Nature communications · 2026Article
- Association between atherosclerotic index of plasma and long-term aortic-related adverse events in type B aortic dissection patients undergoing thoracic endovascular aortic repair.Cardiovascular diabetology · 2026Article
- Aortic dissection: the role of macrophages in disease pathogenesis and their potential as a treatment target.Journal of cardiothoracic surgery · 2026Review
- Prediction value of cystatin C for postoperative acute kidney injury of acute type A aortic dissection.Journal of medical biochemistry · 2026Article
- Integration of single-cell and bulk RNA sequencing data identified an aortic dissection-enriched ANGPTL4+ macrophage subpopulation.Frontiers in immunology · 2026Article
- Hepatic mitochondrial signaling as a systemic hub: inter-organ communication networks in aging and aging-related diseases.Frontiers in cell and developmental biology · 2026Review
- The role of macrophages in aortic physiology and pathophysiology.Frontiers in immunology · 2026Review
- Knowledge, Attitudes, and Practices of Hypertensive Patients with Aortic Dissection and Aortic Aneurysm Towards Aortic Dissection and Its Prevention: A Mediation Analysis.International journal of general medicine · 2026Article
- Aortic dissection as a disease of vascular wall homeostasis: integrating vasa vasorum-inflammation-metabolism axis for mechanistic insight and clinical translation.Frontiers in immunology · 2026Review
- Identification of hub genes in aortic dissection based on weighted gene co-expression network analysis and Mendelian randomization study.Journal of cardiothoracic surgery · 2025Article
- The transcription factor RBPJ is required for inflammatory macrophage activation in thoracic aortic dissection by mediating mechanotransduction-induced glycolysis.Cellular and molecular life sciences : CMLS · 2025Article
- Ursodeoxycholic acid alleviates aortic aneurysm and dissection through the intestinal farnesoid X receptor/ceramide synthase 2 axis.Communications biology · 2025Article
- Analysis of serum levels of HIF-1α and IL-6 in patients with acute stanford type a aortic dissection.Journal of cardiothoracic surgery · 2025Article
- The interplay of ferroptosis and oxidative stress in the pathogenesis of aortic dissection.Frontiers in pharmacology · 2025Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAortic dissection is a severe inflammatory vascular disease with high mortality and limited therapeutic options. The hallmarks of aortic dissection comprise aortic inflammatory cell infiltration and elastic fiber disruption, highlighting the involvement of macrophage. Here a role for macrophage hypoxia-inducible factor 1-alpha (HIF-1α) in aortic dissection was uncovered.
methodsImmunochemistry, immunofluorescence, western blot and qPCR were performed to test the change of macrophage HIF-1α in two kinds of aortic dissection models and human tissues. Metabolomics and Seahorse extracellular flux analysis were used to detect the metabolic state of macrophages involved in the development of aortic dissection. Chromatin Immunoprecipitation (ChIP), enzyme-linked immunosorbent assay (ELISA) and cytometric bead array (CBA) were employed for mechanistic studies.
findingsMacrophages involved underwent distinct metabolic reprogramming, especially fumarate accumulation, thus inducing HIF-1α activation in the development of aortic dissection in human and mouse models. Mechanistic studies revealed that macrophage HIF-1α activation triggered vascular inflammation, extracellular matrix degradation and elastic plate breakage through increased a disintegrin and metallopeptidase domain 17 (ADAM17), identified as a novel target gene of HIF-1α. A HIF-1α specific inhibitor acriflavine elicited protective effects on aortic dissection dependent on macrophage HIF-1α.
interpretationThis study reveals that macrophage metabolic reprogramming activates HIF-1α and subsequently promotes aortic dissection progression, suggesting that macrophage HIF-1α inhibition might be a potential therapeutic target for treating aortic dissection.
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