Impact of Indoxyl Sulfate on Progenitor Cell-Related Neovascularization of Peripheral Arterial Disease and Post-Angioplasty Thrombosis of Dialysis Vascular Access

Wu, Chih‐Cheng; Hung, Szu Chun; Kuo, Ko‐Lin; Tarng, Der Cherng

doi:10.3390/toxins9010025

Cited by 13 publications

(9 citation statements)

References 62 publications

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“…27, 36 Finally, neovascularization has been reported to play an important role in the pathophysiology of AAA, 37 and given that CKD is a clinical phenotype of microvascular disease, it is possible that those with CKD are more likely to have abnormal aortic neovascularization compared to those without CKD. 38 Nonetheless, future studies are needed to explore these and other pathophysiological mechanisms, which may link CKD, particularly albuminuria, to AAA.…”

Section: Discussionmentioning

confidence: 99%

Chronic kidney disease measures and the risk of abdominal aortic aneurysm

et al. 2018

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Background and aims: Despite its strong link to cardiovascular outcomes, the association of chronic kidney disease (CKD) with abdominal aortic aneurysm (AAA) has not been explicitly and comprehensively investigated. Methods: In 10,724 participants in the Atherosclerosis Risk in Communities Study (aged 53–75 years during 1996–1998), we evaluated the associations of two key CKD measures—estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) - with incident AAA (AAA diagnosis in outpatient, hospitalization discharge, or death records). Additionally, we performed a cross-sectional analysis for the CKD measures and ultrasound-based abdominal aortic diameter in 4,258 participants during 2011–2013. Results During a median follow-up of 13.9 years, 347 participants developed AAA. The demographically-adjusted hazard ratio (HR) was 4.44 (95% CI 1.58–12.49) for eGFR <30, 3.29 (1.89–5.72) for 30–44, 2.03 (1.29–3.19) for 45–59, and 1.62 (1.11–2.35) for 60–74 compared to eGFR ≥90 ml/min/1.73m2 and was 2.49 (1.28–4.87) for ACR ≥300, 1.99 (1.40–2.83) for 30–299, and 1.46 (1.08–1.97) for 10–29 compared to ACR <10 mg/g. The associations were generally similar after accounting for additional confounders, such as smoking (although attenuated), or after stratifying by subgroups, including diabetes. The cross-sectional analysis also showed continuous positive associations of these CKD measures with aortic diameter, particularly at the distal aortic segment assessed. Conclusions: Reduced eGFR and elevated albuminuria were independently associated with greater incidence of AAA and greater abdominal aortic diameter. Our results suggest the potential usefulness of CKD measures to identify persons at high risk of AAA and the need to investigate pathophysiological pathways linking CKD to AAA.

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Section: Discussionmentioning

confidence: 99%

Chronic kidney disease measures and the risk of abdominal aortic aneurysm

et al. 2018

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“…According to data provided by Ahmed et al, IS can trigger RBCs shrinkage and RBCs cell membrane scrambling that lead to suicidal erythrocyte death, which can impede microcirculation [ 13 ]. Furthermore, IS impairs endothelial progenitor cells, which lack is connected with thrombotic events after endovascular interventions [ 15 , 16 ]. In recent times, higher level of IS was connected with increased risk for dialysis graft thrombosis and associated with higher number of thrombectomy procedures [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

The Uremic Toxin Indoxyl Sulfate Accelerates Thrombotic Response after Vascular Injury in Animal Models

Karbowska

Kamiński

Marcińczyk

et al. 2017

Toxins

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Chronic kidney disease (CKD) patients are at high risk for thrombotic events. Indoxyl sulfate (IS) is one of the most potent uremic toxins that accumulates during CKD. Even though IS is associated with an increased risk for cardiovascular disease, its impact on thrombotic events still remains not fully understood. The purpose of the study was to evaluate the direct effect of IS on thrombotic process. We examined the impact of acute exposure to IS on thrombus development induced by electric current in Wistar rats, intravital thrombus formation after laser-induced injury in the mice endothelium, coagulation profile, clot formation dynamics, platelet aggregations, and erythrocyte osmotic resistance. IS doses: 10, 30 and 100 mg/kg body weight (b.w.) increased weight of thrombus induced by electric current in dose-dependent manner (p < 0.001). Furthermore, two highest IS doses increased laser-induced thrombus formation observed via confocal system (increase in fluorescence intensity and total thrombus area (p < 0.01)). Only the highest IS dose decreased clotting time (p < 0.01) and increased maximum clot firmness (p < 0.05). IS did not affect blood morphology parameters and erythrocyte osmotic resistance, but augmented collagen-induced aggregation. Obtained data indicate that IS creates prothrombotic state and contributes to more stable thrombus formation. Thus, we concluded that IS may be one of crucial uremic factors promoting thrombotic events in CKD patients.

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“…In patients with CKD, the accumulation of uremic toxin disrupted EPC migration into the endothelium. Wu et al demonstrated that the protein-bound uremic toxin indoxyl sulfate down-regulated endothelial vacuolization by disrupting the effect of HIF-1-alpha [13]. Thus, indoxyl sulfate disrupted EPCs regeneration and endothelial repair.…”

Section: Epcs and Arterial Calcificationmentioning

confidence: 99%

“…EPCs originating from the bone marrow were shown to be an important mechanism in the repair of injured endothelial cells [12]. However, the EPC phenotype was altered under specific pathologic states, such as the accumulation of uremic toxins [13]. The EPCs with osteogenic character were related to the severity of the vascular calcification [14], and the pharmacologic dose of active vitamin D supplement might enhance the expression of calcifying EPCs in CKD patients [15].…”

Section: Introductionmentioning

confidence: 99%

The Role of Vitamin D in Modulating Mesenchymal Stem Cells and Endothelial Progenitor Cells for Vascular Calcification

Hou

Zheng

et al. 2020

IJMS

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Vascular calcification, which involves the deposition of calcifying particles within the arterial wall, is mediated by atherosclerosis, vascular smooth muscle cell osteoblastic changes, adventitial mesenchymal stem cell osteoblastic differentiation, and insufficiency of the calcification inhibitors. Recent observations implied a role for mesenchymal stem cells and endothelial progenitor cells in vascular calcification. Mesenchymal stem cells reside in the bone marrow and the adventitial layer of arteries. Endothelial progenitor cells that originate from the bone marrow are an important mechanism for repairing injured endothelial cells. Mesenchymal stem cells may differentiate osteogenically by inflammation or by specific stimuli, which can activate calcification. However, the bioactive substances secreted from mesenchymal stem cells have been shown to mitigate vascular calcification by suppressing inflammation, bone morphogenetic protein 2, and the Wingless-INT signal. Vitamin D deficiency may contribute to vascular calcification. Vitamin D supplement has been used to modulate the osteoblastic differentiation of mesenchymal stem cells and to lessen vascular injury by stimulating adhesion and migration of endothelial progenitor cells. This narrative review clarifies the role of mesenchymal stem cells and the possible role of vitamin D in the mechanisms of vascular calcification.

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Impact of Indoxyl Sulfate on Progenitor Cell-Related Neovascularization of Peripheral Arterial Disease and Post-Angioplasty Thrombosis of Dialysis Vascular Access

Cited by 13 publications

References 62 publications

Chronic kidney disease measures and the risk of abdominal aortic aneurysm

Chronic kidney disease measures and the risk of abdominal aortic aneurysm

The Uremic Toxin Indoxyl Sulfate Accelerates Thrombotic Response after Vascular Injury in Animal Models

The Role of Vitamin D in Modulating Mesenchymal Stem Cells and Endothelial Progenitor Cells for Vascular Calcification

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