Downregulation of the endothelial histone demethylase JMJD3 is associated with neointimal hyperplasia of arteriovenous fistulas in kidney failure

Feng, Shaozhen; Peden, Eric K.; Guo, Qunying; Lee, Tae Hoon; Li, Qingtian; Yuan, Yuhui; Chen, Changyi; Huang, Fengzhang; Cheng, Jizhong

doi:10.1016/j.jbc.2022.101816

Cited by 3 publications

(2 citation statements)

References 70 publications

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“…Intimal hyperplasia is a key event in AVF dysfunction [ 14 ]. Previous studies showed that pathogenic factors, such as inflammation, oxidative stress, shear stress, and puncture injury, induced an inflammatory cascade reaction, promoted the proliferation of smooth muscle cells, and caused these cells to migrate to the vascular intima, which led to neointimal hyperplasia (NIH) in AVF tissue [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor 21 predicts arteriovenous fistula functional patency loss and mortality in patients undergoing maintenance hemodialysis

Hu,

Ding,

Wei

et al. 2024

Renal Failure

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Background Arteriovenous fistula (AVF) dysfunction is a common complication in patients undergoing maintenance hemodialysis (MHD). Elevated serum levels of fibroblast growth factor 21 (FGF21) are associated with atherosclerosis and cardiovascular mortality. However, its association with vascular access outcomes remains elusive. The present study evaluated the relationship of serum FGF21 levels with AVF dysfunction and all-cause mortality in patients undergoing MHD. Methods We included patients undergoing MHD using AVF from January 2018 to December 2019. FGF21 concentration was detected using enzyme-linked immunosorbent assay. Patients were followed up to record two clinical outcomes, AVF functional patency loss and all-cause mortality. The follow-up period ended on April 30, 2022. Results Among 147 patients, the mean age was 58.49 ± 14.41 years, and the median serum level of FGF21 was 150.15 (70.57–318.01) pg/mL. During the median follow-up period of 40.83 months, the serum level of FGF21 was an independent risk factor for AVF functional patency loss (per 1 pg/mL increase, HR 1.002 [95% CI: 1.001–1.003, p = 0.003]). Patients with higher serum levels of FGF21 were more likely to suffer from all-cause mortality (per 1 pg/mL increase, HR 1.002 [95% CI: 1.000–1.003, p = 0.014]). The optimal cutoffs for FGF21 to predict AVF functional patency loss and all-cause mortality in patients undergoing MHD were 149.98 pg/mL and 146.43 pg/mL, with AUCs of 0.701 (95% CI: 0.606–0.796, p < 0.001) and 0.677 (95% CI: 0.595–0.752, p = 0.002), respectively. Conclusions Serum FGF21 levels were an independent risk factor and predictor for AVF functional patency loss and all-cause mortality in patients undergoing MHD.

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Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor 21 predicts arteriovenous fistula functional patency loss and mortality in patients undergoing maintenance hemodialysis

Hu,

Ding,

Wei

et al. 2024

Renal Failure

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“…Likewise, He et al [ 171 ] showed that KDM6B and miR-93-5p were up-regulated in mice with acute kidney injury (AKI) and that the expression of inflammatory factor TNF-α was reduced through demethylation of H3K27me3, thus alleviating kidney injury. Feng et al [ 172 ] found that low expression of KDM6B could promote neointimal hyperplasia and inflammatory cell infiltration, which might cause vascular stenosis and access failure in renal dialysis patients. Chen et al [ 173 ] found that KDM6A was a key pro-inflammatory factor of diabetic nephropathy (DKD) in db/db mice.…”

Section: Kdms and Inflammatory Diseasesmentioning

confidence: 99%

Histone demethylases in the regulation of immunity and inflammation

Yin

Zhao

et al. 2023

Cell Death Discov.

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Pathogens or danger signals trigger the immune response. Moderate immune response activation removes pathogens and avoids excessive inflammation and tissue damage. Histone demethylases (KDMs) regulate gene expression and play essential roles in numerous physiological processes by removing methyl groups from lysine residues on target proteins. Abnormal expression of KDMs is closely associated with the pathogenesis of various inflammatory diseases such as liver fibrosis, lung injury, and autoimmune diseases. Despite becoming exciting targets for diagnosing and treating these diseases, the role of these enzymes in the regulation of immune and inflammatory response is still unclear. Here, we review the underlying mechanisms through which KDMs regulate immune-related pathways and inflammatory responses. In addition, we also discuss the future applications of KDMs inhibitors in immune and inflammatory diseases.

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The Pathological Mechanisms and Therapeutic Molecular Targets in Arteriovenous Fistula Dysfunction

Yan,

Song,

Zhang

2024

IJMS

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The number of patients with end-stage renal disease (ESRD) requiring hemodialysis is increasing worldwide. Although arteriovenous fistula (AVF) is the best and most important vascular access (VA) for hemodialysis, its primary maturation failure rate is as high as 60%, which seriously endangers the prognosis of hemodialysis patients. After AVF establishment, the venous outflow tract undergoes hemodynamic changes, which are translated into intracellular signaling pathway cascades, resulting in an outward and inward remodeling of the vessel wall. Outward remodeling refers to the thickening of the vessel wall and the dilation of the lumen to accommodate the high blood flow in the AVF, while inward remodeling is mainly characterized by intimal hyperplasia. More and more studies have shown that the two types of remodeling are closely related in the occurrence and development of, and jointly determining the final fate of, AVF. Therefore, it is essential to investigate the underlying mechanisms involved in outward and inward remodeling for identifying the key targets in alleviating AVF dysfunction. In this review, we summarize the current clinical diagnosis, monitoring, and treatment techniques for AVF dysfunction and discuss the possible pathological mechanisms related to improper outward and inward remodeling in AVF dysfunction, as well as summarize the similarities and differences between the two remodeling types in molecular mechanisms. Finally, the representative therapeutic targets of potential clinical values are summarized.

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Downregulation of the endothelial histone demethylase JMJD3 is associated with neointimal hyperplasia of arteriovenous fistulas in kidney failure

Cited by 3 publications

References 70 publications

Fibroblast growth factor 21 predicts arteriovenous fistula functional patency loss and mortality in patients undergoing maintenance hemodialysis

Fibroblast growth factor 21 predicts arteriovenous fistula functional patency loss and mortality in patients undergoing maintenance hemodialysis

Histone demethylases in the regulation of immunity and inflammation

The Pathological Mechanisms and Therapeutic Molecular Targets in Arteriovenous Fistula Dysfunction

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