MicroRNA-21 and Venous Neointimal Hyperplasia of Dialysis Vascular Access

Abstract

Background and objectives There is increasing evidence that microRNAs (miRNAs) play crucial roles in the regulation of neointima formation. However, the translational evidence of the role of miRNAs in dialysis vascular access is limited.Design, setting, participants, & measurements miRNA expression in tissues was assessed by using venous tissues harvested from ten patients on dialysis who received revision or removal surgery, and ten patients who were predialysis and received creation surgery of arteriovenous fistulas served as controls. To extend these findings, 60 patients who received angioplasty of dialysis access were enrolled and the levels of circulating miRNAs were determined before and 2 days after angioplasty. Clinical follow-up was continued monthly for 6 months. The primary outcome of angioplasty cohort was target lesion restenosis within 6 months after angioplasty. ResultsIn the surgery cohort, the expressions of miR-21, miR-130a, and miR-221 were upregulated in stenotic tissues, whereas those of miR-133 and miR-145 were downregulated. In situ hybridization revealed similar expression patterns of these miRNAs, localized predominantly in the neointima region. Twenty eight patients in the angioplasty cohort developed restenosis within 6 months. The levels of circulating miR-21, miR-130a, miR-221, miR-133, and miR-145 significantly increased 2 days after angioplasty. Kaplan-Meier plots showed that patients with an increase of miR-21 expression level .0.35 have a higher risk of patency loss (hazard ratio, 4.45; 95% confidence interval, 1.68 to 11.7). In a multivariable analysis, postangioplasty increase of miR-21 expression was independently associated with restenosis (hazard ratio, 1.20; 95% confidence interval, 1.07 to 1.35 per one unit increase of miR-21 expression level; P=0.001).Conclusions Certain miRNAs are differentially expressed in the stenotic venous segments of dialysis accesses. An increase in blood miR-21 level with angioplasty is associated with a higher risk of restenosis.

Drug-coated balloon versus conventional balloon angioplasty of hemodialysis arteriovenous fistula or graft: A systematic review and meta-analysis of randomized controlled trials

“…Nonetheless, the effect of paclitaxel persisted only for a limited period in the vessel wall. Third, the pathology of vascular access stenosis is predominantly neointimal hyperplasia, which is very different from atherosclerosis [28,29]. Fourth, veins contain less elastic lamina than arteries, which may predispose the migration of smooth muscle cells into neointima [29].…”

Anti Human CX3CR1 VHH Molecule Attenuates Venous Neointimal Hyperplasia of Arteriovenous Fistula in Mouse Model

“…In a separate group of patients, we identified outflow vein segments from stenotic AVFs undergoing surgical revision. 13 This was referred to as AVF. The patient demographics are described in Table 1.…”

The Role of MicroRNA-21 in Venous Neointimal Hyperplasia: Implications for Targeting miR-21 for VNH Treatment

“…We used venous tissue samples from patients with stenosis formation and those undergoing placement of an AVF. 6 , 7 In situ hybridization (ISH) for miR-21 demonstrated that miR-21 expression was significantly increased in stenotic samples compared to non-stenotic samples ( Figures 1 A and 1B). Since smooth muscle and fibroblasts are present in the venous stenosis, we performed immunofluorescence staining, and we found that the majority of the cells that were positive for miR-21 were also positive for fibroblast-specific protein (FSP)-1 ( Figures 1 C and 1D), but not α-smooth muscle cell actin (α-SMA) ( Figures 1 E and 1F), suggesting that miR-21 is in part upregulated by fibroblasts.…”

“…Unstained tissue sections of the outflow veins of functional and failed AVFs from patients who were on hemodialysis were obtained from Dr. Padron Vazquez at the University of Miami Miller School of Medicine (Miami, FL, USA) and Dr. Chin-Wien Wu at the National Taiwan University Hospital (Hsinchu, Taiwan), with institutional review board (IRB) approval. 6 , 7 …”