ArticleJournal of the American Society of Nephrology : JASN2014
Blocking Notch in endothelial cells prevents arteriovenous fistula failure despite CKD.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Endothelial TGF-β Signaling Regulates Endothelial-Mesenchymal Transition During Arteriovenous Fistula Remodeling in Mice With Chronic Kidney Disease.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- The Pathological Mechanisms and Therapeutic Molecular Targets in Arteriovenous Fistula Dysfunction.International journal of molecular sciences · 2024Review
- Article
- Association between preoperative C-reactive protein to albumin ratio and late arteriovenous fistula dysfunction in hemodialysis patients: a cohort study.Scientific reports · 2023Article
- The PPAR-γ Agonist Pioglitazone Modulates Proliferation and Migration in HUVEC, HAOSMC and Human Arteriovenous Fistula-Derived Cells.International journal of molecular sciences · 2023Article
- Endoplasmic Reticulum Stress-induced Endothelial Dysfunction Promotes Neointima Formation after Arteriovenous Grafts in Mice on High-fat Diet.Current medical science · 2023Article
- Temporal regulation of notch activation improves arteriovenous fistula maturation.Journal of translational medicine · 2022Article
- Downregulation of the endothelial histone demethylase JMJD3 is associated with neointimal hyperplasia of arteriovenous fistulas in kidney failure.The Journal of biological chemistry · 2022Article
- Stem cells in the treatment of renal fibrosis: a review of preclinical and clinical studies of renal fibrosis pathogenesis.Stem cell research & therapy · 2021Review
- MMP-9 Deletion Attenuates Arteriovenous Fistula Neointima through Reduced Perioperative Vascular Inflammation.International journal of molecular sciences · 2021Article
- Decreased Jagged1 expression in vascular smooth muscle cells delays endothelial regeneration in arteriovenous graft.Cardiovascular research · 2020Article
- Differences in Transforming Growth Factor-β1/BMP7 Signaling and Venous Fibrosis Contribute to Female Sex Differences in Arteriovenous Fistulas.Journal of the American Heart Association · 2020Article
- Effect of sex differences in treatment response to angioplasty in a murine arteriovenous fistula model.American journal of physiology. Renal physiology · 2020Article
- Single Cell Analysis in Vascular Biology.Frontiers in cardiovascular medicine · 2020Review
- Notch signaling in bone marrow-derived FSP-1 cells initiates neointima formation in arteriovenous fistulas.Kidney international · 2019Article
- High-throughput screening discovers antifibrotic properties of haloperidol by hindering myofibroblast activation.JCI insight · 2019Article
- Elucidating the role of graft compliance mismatch on intimal hyperplasia using an ex vivo organ culture model.Acta biomaterialia · 2019Article
- Abnormalities of vascular histology and collagen fiber configuration in patients with advanced chronic kidney disease.The journal of vascular access · 2019Article
- Jagged1/Notch2 controls kidney fibrosis via Tfam-mediated metabolic reprogramming.PLoS biology · 2018Article
- Reduced Expression of Glutathione S-TransferaseJournal of the American Society of Nephrology : JASN · 2018Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Neointima formation causes the failure of 60% of arteriovenous fistulas (AVFs) within 2 years. Neointima-forming mechanisms are controversial but possibly linked to excess proinflammatory responses and dysregulated Notch signaling. To identify how AVFs fail, we anastomosed the carotid artery to the internal jugular vein in normal and uremic mice and compared these findings with those in failed AVFs from patients with ESRD. Endothelial cells (ECs) of AVFs in uremic mice or patients expressed mesenchymal markers (FSP-1 and/or α-SMA) and exhibited increased expression and nuclear localization of Notch intracellular domain compared with ECs of AVFs in pair-fed control mice. Furthermore, expression of VE-Cadherin decreased, whereas expression of Notch1 and -4, Notch ligands, the downstream transcription factor of Notch, RBP-Jκ, and Notch target genes increased in ECs of AVFs in uremic mice. In cultured ECs, ectopic expression of Notch ligand or treatment with TGF-β1 triggered the expression of mesenchymal markers and induced endothelial cell barrier dysfunction, both of which were blocked by Notch inhibition or RBP-Jκ knockout. Furthermore, Notch-induced defects in barrier function, invasion of inflammatory cells, and neointima formation were suppressed in mice with heterozygous knockdown of endothelial-specific RBP-Jκ. These results suggest that increased TGF-β1, a complication of uremia, activates Notch in endothelial cells of AVFs, leading to accelerated neointima formation and AVF failure. Suppression of Notch activation could be a strategy for improving AFV function in uremia.
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