Serum p -cresyl sulfate predicts cardiovascular disease and mortality in elderly hemodialysis patients

Lin, Cheng‐Jui; Chen, Chuang; Jayakumar, Thanasekaran; Liu, Hsuan‐Liang; Pan, Chi-Feng; Wang, Tuen-Jen; Chen, Han‐Hsiang; Wu, Chih‐Jen

doi:10.5114/aoms.2013.36901

Cited by 45 publications

(39 citation statements)

References 25 publications

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“…The SCFA propionate significantly attenuated cardiac hypertrophy, fibrosis and vascular dysfunction, mainly via regulatory T cells (Bartolomaeus, et al, 2019). Besides the gut metabolites mentioned above, phenyl-acetyl-glutamine (PAG) is a strong and independent risk factor for CVD and mortality (Poesen, et al, 2016), and p-cresyl sulfate (PCS) might function as a predictor of cardiovascular events and allcause mortality (Lin, et al, 2013) (Table 1).…”

Section: Heart Failure and Cardiomyopathymentioning

confidence: 99%

The gut microbiota and its interactions with cardiovascular disease

Wang

Feng

et al. 2020

Microbial Biotechnology

104

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Summary The intestine is colonized by a considerable community of microorganisms that cohabits within the host and plays a critical role in maintaining host homeostasis. Recently, accumulating evidence has revealed that the gut microbial ecology plays a pivotal role in the occurrence and development of cardiovascular disease (CVD). Moreover, the effects of imbalances in microbe–host interactions on homeostasis can lead to the progression of CVD. Alterations in the composition of gut flora and disruptions in gut microbial metabolism are implicated in the pathogenesis of CVD. Furthermore, the gut microbiota functions like an endocrine organ that produces bioactive metabolites, including trimethylamine/trimethylamine N‐oxide, short‐chain fatty acids and bile acids, which are also involved in host health and disease via numerous pathways. Thus, the gut microbiota and its metabolic pathways have attracted growing attention as a therapeutic target for CVD treatment. The fundamental purpose of this review was to summarize recent studies that have illustrated the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors. Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.

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Section: Heart Failure and Cardiomyopathymentioning

confidence: 99%

The gut microbiota and its interactions with cardiovascular disease

Wang

Feng

et al. 2020

Microbial Biotechnology

104

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“…The association of PCS with CVD has also been reported [45–47]. Thus it would be interesting to evaluate the effects of PCS and PhS in vascular cells.…”

Section: Discussionmentioning

confidence: 89%

Classification of Five Uremic Solutes according to Their Effects on Renal Tubular Cells

Edamatsu

Fujieda

Ezawa

et al. 2014

International Journal of Nephrology

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Background/Aims. Uremic solutes, which are known to be retained in patients with chronic kidney disease, are considered to have deleterious effects on disease progression. Among these uremic solutes, indoxyl sulfate (IS) has been extensively studied, while other solutes have been studied less to state. We conducted a comparative study to examine the similarities and differences between IS, p-cresyl sulfate (PCS), phenyl sulfate (PhS), hippuric acid (HA), and indoleacetic acid (IAA). Methods. We used LLC-PK1 cells to evaluate the effects of these solutes on viable cell number, cell cycle progression, and cell death. Results. All the solutes reduced viable cell number after 48-hour incubation. N-Acetyl-L-cysteine inhibited this effect induced by all solutes except HA. At the concentration that reduced the cell number to almost 50% of vehicle control, IAA induced apoptosis but not cell cycle delay, whereas other solutes induced delay in cell cycle progression with marginal impact on apoptosis. Phosphorylation of p53 and Chk1 and expression of ATF4 and CHOP genes were detected in IS-, PCS-, and PhS-treated cells, but not in IAA-treated cells. Conclusions. Taken together, the adverse effects of PCS and PhS on renal tubular cells are similar to those of IS, while those of HA and IAA differ.

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“…PCS is a newly identified uremic toxin which has been associated with CKD progression and with cardiovascular disease and mortality risk (Wu et al, ; Lin et al, ; Lin et al, ; Lin et al, ). In the vasculature, PCS has been demonstrated to induce an inflammatory process, mainly by increasing ROS production in endothelial cells and leukocytes (Schepers et al, ; Itoh et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…All available clinical studies on PCS, whether in hemodialysis or in CKD patients not yet on dialysis therapy, reported a strong association with cardiovascular mortality as well as with vascular disease (Wu et al, ; Lin et al, ; Lin et al, ; Lin et al, ).…”

mentioning

confidence: 99%

Para‐cresyl sulfate acutely impairs vascular reactivity and induces vascular remodeling

Gross

Massy

Hénaut

et al. 2015

Journal Cellular Physiology

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Chronic kidney disease (CKD) is characterized by vascular remodeling and the retention of uremic toxins, several of which are independently associated with the high cardiovascular mortality rate in CKD patients. Whether the association between these uremic toxins and cardiovascular mortality is due to induction of vascular dysfunction and resulting vascular remodeling remains to be determined. This study evaluates the effects of para-cresyl sulfate (PCS), a newly identified uremic toxin, on vascular function and remodeling. PCS acutely induced oxidative stress in both endothelial and vascular smooth muscle cells, with a maximal effect at 0.15 mM, corresponding to the mean "uremic" concentration found in dialysis patients. PCS significantly increased within 30 min phenylephrine-induced contraction of mouse thoracic aorta, through direct activation of rho-kinase, independently of oxidative stress induction, as demonstrated by the capacity of rho-kinase inhibitor Y-27632 to abolish this effect. After exposure of the aorta to PCS for 48 h, we observed inward eutrophic remodeling, a hallmark of uremic vasculopathy characterized by a reduction of the area of both lumen and media, with unchanged media/lumen ratio. In conclusion, elevated PCS concentrations such as those observed in CKD patients, by promoting both vascular dysfunction and vascular remodeling, may contribute to the development of hypertension and to cardiovascular mortality in CKD.

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Serum p -cresyl sulfate predicts cardiovascular disease and mortality in elderly hemodialysis patients

Cited by 45 publications

References 25 publications

The gut microbiota and its interactions with cardiovascular disease

The gut microbiota and its interactions with cardiovascular disease

Classification of Five Uremic Solutes according to Their Effects on Renal Tubular Cells

Para‐cresyl sulfate acutely impairs vascular reactivity and induces vascular remodeling

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