Role of crosstalk between endothelial cells and smooth muscle cells in vascular calcification in chronic kidney disease

Zhang, Yu-Xia; Tang, Ri‐Ning; Wang, Liting; Liu, Bi‐Cheng

doi:10.1111/cpr.12980

Cited by 28 publications

(20 citation statements)

References 82 publications

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“…Vascular calcification is a controllable and reversible pathophysiological process similar to the formation of bone and cartilage. Under the induced stimulation, vascular endothelial cells and smooth muscle cells can differentiate into chondroid cells, accompanied by calcium and phosphorus deposition in the vascular wall [ 42 ]. At present, some proteins such as vitamin K-dependent calcification inhibitory proteins [ 43 ], bone morphogenetic proteins [ 44 ], and sclerostin proteins [ 45 ] have been found to be involved in the regulation of vascular calcification.…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNA-29b and Sclerostin Levels Correlate with Coronary Artery Calcification and Cardiovascular Events in Maintenance Hemodialysis Patients

Pan

et al. 2021

Cardiology Research and Practice

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Objective. Coronary artery calcification (CAC) is a common complication in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (MHD), and the extent of CAC is a predominant predictor of cardiovascular outcomes in MHD patients. In this study, we sought to uncover the relationship between circulating miRNA-29b, sclerostin levels, CAC, and cardiovascular events (CVEs) in MHD patients. Methods. This study recruited patients receiving MHD for at least three months in the Hainan General Hospital between January 2016 and June 2019, and all patients were followed up 24 months for CVEs. The serum level of sclerostin was determined by enzyme-linked immunosorbent assay (ELISA) and miRNA-29b expression by real-time qPCR (RT-qPCR). All patients received cardiac CT scans to evaluate CAC, and CAC scores were expressed in Agatston units. The MHD patients with CACs <100 were arranged into the CAC (<100) group, those with 100–400 CACs into the CAC (100–400) group, and those with CACs >400 into the CAC (>400) group. Net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to assess the predictive performance of serum sclerostin level for the occurrence of CVEs. Results. Compared with the CAC (<100) group, the CAC (>400) group had higher proportions of older patients, hypertension and diabetes mellitus patients, longer dialysis duration, higher mean arterial pressure (MAP), higher levels of high-sensitivity C-reactive protein (hs-CRP), alkaline phosphatase (ALP), and phosphate ( P < 0.05 ). It was found that the CAC (100–400) and CAC (>400) groups exhibited higher serum levels of sclerostin but lower levels of miRNA-29b than the CAC (<100) group ( P < 0.05 ) and the CAC (>400) group had a higher level of sclerostin and a lower level of miRNA-29b than the CAC (100–400) group ( P < 0.05 ). The circulating level of miRNA-29b was negatively correlated with the serum level of sclerostin in MHD patients (r = −0.329, P < 0.01 ). The multivariate logistic regression analysis showed that hs-CRP, phosphate, sclerostin, and miRNA-29b were independent risk factors for CAC in MHD patients ( P < 0.05 , Table 2). ROC for prediction of CAC by sclerostin yielded 0.773 AUC with 95% CI 0.683–0.864 ( P < 0.01 ). As depicted by Kaplan–Meier curves of CVE incidence in MHD patients according to median sclerostin (491.88 pg/mL) and median miRNA-29b (Ct = 25.15), we found that serum levels of sclerostin and miRNA-29b were correlated with the incidence of CVEs in MHD patients. When a new model was used to predict the incidence of CVEs, NRI 95% CI was 0.60 (0.16–1.03) ( P < 0.05 ) and IDI 95% CI was 0.002 (−0.014 to 0.025) ( P < 0.05 ), suggesting that sclerostin added into the old model could improve the prediction of the incidence of CVEs. Conclusions. These data suggest that circulating miRNA-29b and sclerostin levels are correlated with CAC and incidence of CVEs in MHD patients. Higher sclerostin and lower miRNA-29b may serve as independent risk factors for the incidence of CVEs in MHD patients.

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Section: Discussionmentioning

confidence: 99%

Circulating miRNA-29b and Sclerostin Levels Correlate with Coronary Artery Calcification and Cardiovascular Events in Maintenance Hemodialysis Patients

Pan

et al. 2021

Cardiology Research and Practice

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“…Also of importance, our mouse model does not recapitulate the environment of chronic kidney disease, which may induce EndMT via inflammation or oxidative stress. 42 Both cell-specific and pan-inhibition of TGF-β signaling showed inhibitory effects on ECM deposition. These data suggest that differences in AVF wall thickness are attributable to the effects of TGF-β on SMC proliferation.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Cell TGF-β (Transforming Growth Factor-Beta) Signaling Regulates Venous Adaptive Remodeling to Improve Arteriovenous Fistula Patency

Taniguchi

Ohashi

Lee

et al. 2022

ATVB

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BACKGROUND: Arteriovenous fistulae (AVF) are the gold standard for vascular access for hemodialysis. Although the vein must thicken and dilate for successful hemodialysis, excessive wall thickness leads to stenosis causing AVF failure. Since TGF-β (transforming growth factor-beta) regulates ECM (extracellular matrix) deposition and smooth muscle cell (SMC) proliferation—critical components of wall thickness—we hypothesized that disruption of TGF-β signaling prevents excessive wall thickening during venous remodeling. METHODS: A mouse aortocaval fistula model was used. SB431542—an inhibitor of TGF-β receptor I—was encapsulated in nanoparticles and applied to the AVF adventitia in C57BL/6J mice. Alternatively, AVFs were created in mice with conditional disruption of TGF-β receptors in either SMCs or endothelial cells. Doppler ultrasound was performed serially to confirm patency and to measure vessel diameters. AVFs were harvested at predetermined time points for histological and immunofluorescence analyses. RESULTS: Inhibition of TGF-β signaling with SB431542-containing nanoparticles significantly reduced p-Smad2–positive cells in the AVF wall during the early maturation phase (days 7–21) and was associated with decreased AVF wall thickness that showed both decreased collagen density and decreased SMC proliferation. SMC-specific TGF-β signaling disruption decreased collagen density but not SMC proliferation or wall thickness. Endothelial cell–specific TGF-β signaling disruption decreased both collagen density and SMC proliferation in the AVF wall and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency. CONCLUSIONS: Endothelial cell–targeted TGF-β inhibition may be a translational strategy to improve AVF patency.

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“…Many studies have gradually found that ECs also have the potential to undergo osteochondrogenic differentiation to promote vascular calcifications [59]. The expression of ossification-related genes in ECs was previously significantly altered under atherogenic and pro-inflammatory stimuli in vitro [60].…”

Section: Phosphate Ckd-mbd Axis and Neurovascular Dysfunctionmentioning

confidence: 99%

Phosphate in the Context of Cognitive Impairment and Other Neurological Disorders Occurrence in Chronic Kidney Disease

Rroji

Figurek

Viggiano

et al. 2022

IJMS

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The nervous system and the kidneys are linked under physiological states to maintain normal body homeostasis. In chronic kidney disease (CKD), damaged kidneys can impair the central nervous system, including cerebrovascular disease and cognitive impairment (CI). Recently, kidney disease has been proposed as a new modifiable risk factor for dementia. It is reported that uremic toxins may have direct neurotoxic (astrocyte activation and neuronal death) and/or indirect action through vascular effects (cerebral endothelial dysfunction, calcification, and inflammation). This review summarizes the evidence from research investigating the pathophysiological effects of phosphate toxicity in the nervous system, raising the question of whether the control of hyperphosphatemia in CKD would lower patients’ risk of developing cognitive impairment and dementia.

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Role of crosstalk between endothelial cells and smooth muscle cells in vascular calcification in chronic kidney disease

Cited by 28 publications

References 82 publications

Circulating miRNA-29b and Sclerostin Levels Correlate with Coronary Artery Calcification and Cardiovascular Events in Maintenance Hemodialysis Patients

Circulating miRNA-29b and Sclerostin Levels Correlate with Coronary Artery Calcification and Cardiovascular Events in Maintenance Hemodialysis Patients

Endothelial Cell TGF-β (Transforming Growth Factor-Beta) Signaling Regulates Venous Adaptive Remodeling to Improve Arteriovenous Fistula Patency

Phosphate in the Context of Cognitive Impairment and Other Neurological Disorders Occurrence in Chronic Kidney Disease

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