Objective: To investigate the association of short-term blood pressure variability (BPV) with cardiovascular mortality in hemodialysis (HD) patients, using a reliable index called average real variability (ARV), and to assess the factors associated with ARV in incident HD population.Methods: A total of 103 HD patients were recruited, with 44-h ambulatory blood pressure monitoring performed after the midweek HD session. Systolic BPV was assessed by SD, coefficient of variation (CV), and ARV, respectively. Laboratory data were obtained from blood samples before the midweek HD. All patients were followed up for 24 months.Results: According to the median of BPV indices, the comparisons between patients with the low and high values were conducted. Kaplan–Meier analysis showed the survival curves corresponding to median of SD and CV exhibit similar performance for the low and high groups (p = .647, p = .098, respectively). In contrast, patients with higher ARV had a lower survival rate than those with lower ARV (77.8% vs. 98.0%, p = .002). After adjustment for demographics and clinical factors, ARV (HR: 1.143; 95% CI: 1.022–1.279, p = .019) and high-sensitivity C-reactive protein (HR: 1.394; 95% CI: 1.025–1.363, p = .021) were associated with increased risk of cardiovascular mortality in HD patients. Age and interdialytic weight gain (IDWG) were related factors for ARV (β = 0.065, p = .005; β = 0.825, p = .003, respectively).Conclusions: Greater ARV was independently associated with increased risk of cardiovascular mortality in HD patients. Age and IDWG were independent related factors for ARV.
Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is considered to be an independent risk factor in the progression of chronic kidney diseases (CKD). It can induce kidney fibrosis by increasing transforming growth factor (TGF)-β1 expression, but its molecular mechanism is unclear. The aim of the present study was to investigate the role of actin cytoskeleton in ADMA-induced TGF-β1 high expression in human renal glomerular endothelial cells (HRGECs). The structure of stress fibers was visualized by immunofluorescence, nuclear factor-κB (NF-κB) DNA-binding activity was assessed by an electrophoretic mobility shift assay and TGF-β1 expression was assessed by western blot analysis. Results showed that ADMA induced the assembly of stress fibers, DNA binding of NF-κB, and increasing expression of TGF-β1. When the dynamics of actin cytoskeleton was perturbed by the actin-depolymerizing agent cytochalasin D and the actin-stabilizing agent jasplakinolide, or ablation of stress fiber bundles by the nicotineamide adenine dinucleotide phosphate oxidase inhibitor apocynin and p38 mitogen-activated protein kinase inhibitor SB203580, ADMA-induced DNA binding of NF-κB and TGF-β1 expression were inhibited. These results revealed an actin cytoskeleton-dependent mechanism in ADMA-induced NF-κB activation and TGF-β1 high expression in HRGECs. The specific targeting of the actin cytoskeleton may be a useful strategy to prevent ADMA-activated kidney fibrosis in CKD.
Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, accumulates in plasma during chronic kidney disease (CKD). High plasma levels of ADMA can increase transforming growth factor-β (TGF-β) expression, related to renal fibrosis, but the precise molecular mechanism is not explicit. The present study was designed to determine the mechanism through which long-term low-dose ADMA induces TGF-β expression in endothelial cells and to investigate the molecular mechanism of its action. Human umbilical vein endothelial cells (HUVECs) were exposed to low-dose ADMA (5 and 10 µmol/l) for 7 passages and TGF-β expression was determined. Human renal glomerular endothelial cells (HRGECs) were exposed to high-dose ADMA (100 µmol/l) which were used to clarify the molecular mechanism. The results showed that long-term low-dose ADMA (5 and 10 µmol/l) increases TGF-β production in both mRNA and protein levels in HUVECs in a time-dependent manner. We confirmed that exogenous ADMA (100 µmol/l) significantly enhanced stress fiber formation in HRGECs and upregulated TGF-β expression. Such effects of ADMA in HRGECs were inhibited by pre-treatment with actin depolymerizing agent, actin stabilizing agent, p38 MAPK inhibitor and NADPH oxidase inhibitor. In addition, we demonstrated that ADMA (100 µmol/l) significantly activated nuclear factor-κB (NF-κB) in HRGECs, which was markedly attenuated by actin depolymerizing agent, actin stabilizing agent, p38 MAPK inhibitor and NADPH oxidase inhibitor. In brief, the present study demonstrated that long-term low-dose ADMA induces TGF-β expression in endothelial cells at both the gene and protein levels. The actin cytoskeleton may be involved in modulation of ADMA-induced NF-κB activation and the ensuing TGF-β expression in HRGECs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.