title: Migration of smooth muscle cells from the arterial anastomosis of arteriovenous fistulas requires Notch activation to form neointima.
abstract: A major factor contributing to failure of arteriovenous fistulas (AVFs) is migration of smooth muscle cells into the forming neointima. To identify the source of smooth muscle cells in neointima, we created end-to-end AVFs by anastomosing the common carotid artery to the jugular vein and studied neural crest-derived smooth muscle cells from the carotid artery, which are Wnt1-positive during development. In Wnt1-cre-GFP mice, smooth muscle cells in the carotid artery but not the jugular vein are labeled with GFP. About half of the cells were GFP-positive in the neointima, indicating their migration from the carotid artery to the jugular vein in AVFs created in these mice. As fibroblast-specific protein-1 (FSP-1) regulates smooth muscle cell migration, we examined FSP-1 in failed AVFs and polytetrafluoroethylene grafts from patients with end-stage kidney disease or from AVFs in mice with chronic kidney disease. In smooth muscle cells of AVFs or polytetrafluoroethylene grafts, FSP-1 and activation of Notch1 are present. In smooth muscle cells, Notch1 increased RBP-Jκ transcription factor activity and RBP-Jκ stimulated FSP-1 expression. Conditional knockout of RBP-Jκ in smooth muscle cells or general knockout of FSP-1 suppressed neointima formation in AVFs in mice. Thus, the artery of AVFs is the major source of smooth muscle cells during neointima formation. Knockout of RBP-Jκ or FSP-1 ameliorates neointima formation and might improve AVF patency during long-term follow-up.
authors.affiliation: Department of Nephrology, Guangzhou First People's Hospital, Guangzhou Medical University, China.|Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Liang
authors.affiliation: Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Anlin
authors.initials: A
authors.lastname: Liang
authors.affiliation: Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Mitch
authors.affiliation: Department of Surgery, Pathology and Radiology and Division of Nephrology, Department of Medicine, University of Cincinnati and Cincinnati VAMC, Cincinnati, Ohio, USA.
authors.forename: Prabir
authors.initials: P
authors.lastname: Roy-Chaudhury
authors.affiliation: Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.|The 455th Hospital, Shanghai, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Han
authors.affiliation: Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000368:Aged; D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects* / Q000295:instrumentation; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002465:Cell Movement; D002478:Cells, Cultured; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism; D007601:Jugular Veins / Q000601:surgery; D008297:Male; D008822:Mice, Transgenic; D008875:Middle Aged; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D058426:Neointima; D034622:RNA Interference; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000628:therapy*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014654:Vascular Patency
chemical_list: D002135:Calcium-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; C497570:RBPJ protein, human; C497571:Rbpj protein, mouse; D051881:Receptor, Notch1; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C077591:S100A4 protein, human