Dataset Information

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.

Results

In 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.

SUBMITTER: Wu CC

PROVIDER: S-EPMC6237050 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

MicroRNA-21 and Venous Neointimal Hyperplasia of Dialysis Vascular Access.

Wu Chih-Cheng CC Chen Li-Jing LJ Hsieh Mu-Yang MY Lo Chien-Ming CM Lin Ming-Hsien MH Tsai Hsiao-En HE Song Hsiang-Lin HL Chiu Jeng-Jiann JJ

Clinical journal of the American Society of Nephrology : CJASN 20180921 11

<h4>Background and objectives</h4>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.<h4>Design, setting, participants, & measurements</h4>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 cre ...[more]

PMID: 30242025

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Project description:In patients with severe kidney disease AVF are surgically placed in order to create good access for hemodialysis. In these dialysis patients the failure rates of AVF can be as high as 24% within 6 months after surgery, causing ineffective dialysis and necessitating additional clinical interventions. The pathological processes known to lead to AVF failure are beginning to be unravelled include the formation of venous neointimal hyperplasia (VNIH), thrombosis (Chang et al. PMID 16105066), and venous stenosis (Kanterman et al. PMID7892454, Tang et al. 1998), resulting in a reduced blood flow through the fistula. We established a rat model for AVF failure in human kidney dialysis patients. The characterization of this model has been previously described (Globerman et al. 2011, PubmedID:22002501). In this model the AVFs are surgically constructed in the right leg by connecting the superficial epigastric vein SEV to the common femoral artery (CFA), resulting in exposure of the SEV to arterial pressure with pulsatile and low resistant flow patterns (Globerman et al. 2011, PMID22002501). In the present study we utilized this AVF model in order to assess the effects of arterialized flow, with consequent pathological changes of the vessel wall due to surgical AVF instalment, on the transcriptome of endothelium from the SEV. Within the SEV these pathologies of the vessel wall include the formation of NIH in the main branch, and stenosis in the side branches. By employing this rat model we assessed the changes of the endothelial transcriptome in relation to these pathologies in order to gain mechanistic understanding of the potential roles of venous endothelium in AVF failure, as well as to identify potential biomarkers preceding AVF failure. AVF surgery was performed on N=6 rats, and 13-14 days after surgery the rats were sacrificed. AVFs were extracted from the rats, and microarray transcriptome analyses were performed on luminal endothelial cells that isolated from four different sites of the AVF by employing Laser Capture Microdissection (LCM). These sites included (i) N=5 AVF sections of the superficial epigastric vein (SEV) with neointimal hyperplasia (NIH), (ii) N=3 AVF sections of SEV side branches with luminal stenosis, (iii), N=6 sections of the SEV located distally from a ligation thereby omitting exposure to arterialized flow and consequently preventing the development of NIH or stenosis, and (iv) N=3 sections of the AVF common femoral artery without signs of NIH or stenosis.

Project description:Introduction: We recently showed that a decellularized leaf scaffold can be loaded with polylactic-co-glycolic acid (PLGA)-based rapamycin nanoparticles, this leaf patch can then inhibit venous neointimal hyperplasia in a rat inferior vena cava (IVC) venoplasty model. IL-33 plays a role in the neointimal formation after vascular injury. We hypothesized that plant leaves can absorb therapeutic drug solution and can be used as a patch with drug delivery capability, and plant leaves absorbed with IL-33 antibody can decrease venous neointimal hyperplasia in the rat IVC venoplasty model. Method: A human spiral saphenous vein (SVG) graft implanted in the popliteal vein was harvested from a patient with trauma and analyzed by immunofluorescence. Male Sprague-Dawley rats (aged 6-8 weeks) were used to create the IVC patch venoplasty model. Plant leaves absorbed with rhodamine, distilled water (control), rapamycin, IL-33, and IL-33 antibody were cut into patches (3 × 1.5 mm2) and implanted into the rat IVC. Patches were explanted at day 14 for analysis. Result: At day 14, in the patch absorbed with rhodamine group, immunofluorescence showed rhodamine fluorescence in the neointima, inside the patch, and in the adventitia. There was a significantly thinner neointima in the plant patch absorbed with rapamycin (p = 0.0231) compared to the patch absorbed with distilled water. There was a significantly large number of IL-33 (p = 0.006) and IL-1β (p = 0.012) positive cells in the human SVG neointima compared to the human great saphenous vein. In rats, there was a significantly thinner neointima, a smaller number of IL-33 (p = 0.0006) and IL-1β (p = 0.0008) positive cells in the IL-33 antibody-absorbed patch group compared to the IL-33-absorbed patch group. Conclusion: We found that the natural absorption capability of plant leaves means they can absorb drug solution efficiently and can also be used as a novel drug delivery system and venous patch. IL-33 plays a role in venous neointimal hyperplasia both in humans and rats; neutralization of IL-33 by IL-33 antibody can be a therapeutic method to decrease venous neointimal hyperplasia.

Dataset Information

MicroRNA-21 and Venous Neointimal Hyperplasia of Dialysis Vascular Access.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Publications

MicroRNA-21 and Venous Neointimal Hyperplasia of Dialysis Vascular Access.

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