Dataset Information

Simvastatin reduces venous stenosis formation in a murine hemodialysis vascular access model.

ABSTRACT: Venous neointimal hyperplasia (VNH) is responsible for hemodialysis vascular access malfunction. Here we tested whether VNH formation occurs, in part, due to vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase (MMP)-9 gene expression causing adventitial fibroblast transdifferentiation to myofibroblasts (?-SMA-positive cells). These cells have increased proliferative and migratory capacity leading to VNH formation. Simvastatin was used to decrease VEGF-A and MMP-9 gene expression in our murine arteriovenous fistula model created by connecting the right carotid artery to the ipsilateral jugular vein. Compared to fistulae of vehicle-treated mice, the fistulae of simvastatin-treated mice had the expected decrease in VEGF-A and MMP-9 but also showed a significant reduction in MMP-2 expression with a significant decrease in VNH and a significant increase in the mean lumen vessel area. There was an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and decreases in ?-SMA density, cell proliferation, and HIF-1? and hypoxyprobe staining. This latter result prompted us to determine the effect of simvastatin on fibroblasts subjected to hypoxia in vitro. Simvastatin-treated fibroblasts had a significant decrease in myofibroblast production along with decreased cellular proliferation, migration, and MMP-9 activity but increased caspase 3 activity suggesting increased apoptosis. Thus, simvastatin results in a significant reduction in VNH, with increase in mean lumen vessel area by decreasing VEGF-A/MMP-9 pathway activity.

SUBMITTER: Janardhanan R

PROVIDER: S-EPMC3731558 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Simvastatin reduces venous stenosis formation in a murine hemodialysis vascular access model.

Janardhanan Rajiv R Yang Binxia B Vohra Pawan P Roy Bhaskar B Withers Sarah S Bhattacharya Santanu S Mandrekar Jaywant J Kong Hyunjoon H Leof Edward B EB Mukhopadhyay Debabrata D Misra Sanjay S

Kidney international 20130501 2

Venous neointimal hyperplasia (VNH) is responsible for hemodialysis vascular access malfunction. Here we tested whether VNH formation occurs, in part, due to vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase (MMP)-9 gene expression causing adventitial fibroblast transdifferentiation to myofibroblasts (α-SMA-positive cells). These cells have increased proliferative and migratory capacity leading to VNH formation. Simvastatin was used to decrease VEGF-A and MMP-9 gene expr ...[more]

PMID: 23636169

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Project description:Background and objectivesMedicare reimbursement policy encourages frequent provider visits to patients with ESRD undergoing hemodialysis. This study sought to determine whether more frequent face-to-face provider (physician and advanced practitioner) visits lead to more procedures and therapeutic interventions aimed at preserving arteriovenous fistulas and grafts, improved vascular access outcomes, and fewer related hospitalizations.Design, setting, participants, & measurementsMultivariable regression was used to evaluate the association between provider (physician and advanced practitioner) visit frequency and interventions aimed at preserving vascular access, vascular access survival, hospitalization for vascular access infection, and outpatient antibiotic use in a cohort of 63,488 Medicare beneficiaries receiving hemodialysis in the United States. Medicare claims were used to identify the type of vascular access used, access-related events, and vascular access failure.ResultsOne additional provider (physician and advanced practitioner) visit per month was associated with a 13% higher odds of receiving an intervention to preserve vascular access (95% confidence interval [95% CI], 12% to 14%) but was not associated with vascular access survival (hazard ratio, 1.01; 95% CI, 0.99 to 1.03). One additional provider visit was associated with a 9% (95% CI, 5% to 14%) lower odds of hospitalization for vascular access infection and a corresponding 9% (95% CI, 5% to 14%) higher odds of outpatient intravenous antibiotic administration. However, the associated changes in absolute probabilities of hospitalization and antibiotic administration were small.ConclusionsMore frequent face-to-face provider (physician and advanced practitioner) visits were associated with more procedures and therapeutic interventions aimed at preserving vascular accesses, but not with prolonged vascular access survival and only a small decrease in hospitalization for vascular access.

Dataset Information

Simvastatin reduces venous stenosis formation in a murine hemodialysis vascular access model.

Publications

Simvastatin reduces venous stenosis formation in a murine hemodialysis vascular access model.

Similar Datasets

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