Role of uremic toxin indoxyl sulfate in the progression of cardiovascular disease

The prevalence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) is relatively high. Deterioration of renal function in CKD leads to accumulation of indoxyl sulfate, a tryptophan metabolite produced by gut microbiota. It is acknowledged that indoxyl sulfate is capable...

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Bibliographic Details
Published in:Life sciences (1973) 2017-09, Vol.185, p.23-29
Main Authors: Gao, Huichang, Liu, Shan
Format: Article
Language:English
Subjects:
Animals
Arrhythmia
Arteriosclerosis
Atherosclerosis
Calcification
Calcification (ectopic)
Cardiomyopathy
Cardiovascular disease
Cardiovascular diseases
Cardiovascular Diseases - physiopathology
Cardiovascular system
Coronary artery
Coronary artery disease
Coronary Artery Disease - physiopathology
Disease Progression
Flora
Heart diseases
Humans
Indican - metabolism
Indoxyl sulfate
Intestinal microflora
Kidney diseases
Kidney transplantation
Microorganisms
NAD(P)H oxidase
NADPH Oxidases - metabolism
Oxidation-Reduction
Oxidative stress
Oxidative Stress - physiology
Pathophysiology
Renal function
Renal Insufficiency, Chronic - physiopathology
Signaling
Studies
Sulfates
Tryptophan
Vascular disease
Vascular diseases
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Summary:The prevalence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) is relatively high. Deterioration of renal function in CKD leads to accumulation of indoxyl sulfate, a tryptophan metabolite produced by gut microbiota. It is acknowledged that indoxyl sulfate is capable to stimulate oxidative stress, which in turn contributes to the progression of vascular disorders and its resultant coronary artery disease. Recent research have demonstrated the adverse effects of indoxyl sulfate on the heart, together with the acceleration of vascular dysfunction, suggesting that indoxyl sulfate might contribute to high prevalence of CVD in CKD. The present mini review has focused on the potential mechanisms by which indoxyl sulfate exerts this pro-oxidant effects on the cardiovascular system. The action of indoxyl sulfate are related to multiple NADPH oxidase-mediated redox signaling pathways, which have been implicated in the pathophysiology of different forms of CVD, including chronic heart failure, arrhythmia, atherosclerotic vascular disease and coronary calcification. Future therapeutic options are discussed, including modulating gut microbial flora and blocking responsible pathophysiologic pathways.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2017.07.027