Smooth Muscle Nitric Oxide Responsiveness and Clinical Maturation of Hemodialysis Arteriovenous Fistulae
| Autor: | Xiuyun Hou, Tal Kopel, Xiaoyong Tong, Christopher Wason, Laura M. Dember, Richard A. Cohen |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Vascular smooth muscle SERCA Smooth muscle cell migration medicine.medical_treatment Down-Regulation Arteriovenous fistula 030204 cardiovascular system & hematology Nitric Oxide Muscle Smooth Vascular Article Sarcoplasmic Reticulum Calcium-Transporting ATPases Pathology and Forensic Medicine Nitric oxide 03 medical and health sciences chemistry.chemical_compound Arteriovenous Shunt Surgical 0302 clinical medicine Cell Movement Renal Dialysis Internal medicine medicine Humans Aged Cell Proliferation Neointimal hyperplasia business.industry NADPH Oxidases Middle Aged medicine.disease Surgery Calcium ATPase 030104 developmental biology Endocrinology chemistry Kidney Failure Chronic Female Hemodialysis business |
| Zdroj: | The American Journal of Pathology. 187:2095-2101 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2017.05.006 |
| Popis: | The arteriovenous fistula is the preferred type of hemodialysis vascular access for patients with end-stage renal disease, but a high proportion of newly created fistulas fail to mature for use. Stenosis caused by neointimal hyperplasia often is present in fistulas with maturation failure, suggesting that local mechanisms controlling vascular smooth muscle cell (SMC) migration and proliferation are important contributors to maturation failure. SMCs cultured from explants of vein tissue obtained at the time of fistula creation from 19 patients with end-stage renal disease were studied to determine whether smooth muscle responsiveness to nitric oxide is associated with fistula maturation outcomes. Nitric oxide–induced inhibition of smooth muscle cell migration, but not proliferation, was greater in cells from patients with subsequent fistula maturation success than from patients with subsequent fistula maturation failure (mean inhibition percentage, 17 versus 5.7, respectively; P = 0.035). Impaired nitric oxide responsiveness was associated with oxidation of the calcium regulatory protein, sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), and was reversed by overexpressing SERCA (1.8-fold increase in inhibition, P = 0.0128) or down-regulating Nox4-based NADPH oxidase (2.3-fold increase in inhibition; P = 0.005). Our data suggest that the nitric oxide responsiveness of SMC migration is associated with fistula maturation success and raises the possibility that therapeutic restoration of nitric oxide responsiveness through manipulation of local mediators may prevent fistula maturation failure. |
| Databáze: | OpenAIRE |
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