Deleterious vascular effects of indoxyl sulfate and reversal by oral adsorbent AST-120

Abstract Background In chronic kidney disease (CKD), blood vessels are permanently exposed to uremic toxins such as indoxyl sulfate (IS). We hypothesized that IS could alter vascular tone and that reducing its serum concentration could be beneficial. Design We studied acute and longer-term effects o...

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Bibliographic Details
Published in:Atherosclerosis 2015-11, Vol.243 (1), p.248-256
Main Authors: Six, Isabelle, Gross, Priscilla, Rémond, Mathieu C, Chillon, Jean Marc, Poirot, Sabrina, Drueke, Tilman B, Massy, Ziad A
Format: Article
Language:English
Subjects:
Administration, Oral
Adsorption
Animals
Aorta - pathology
Apolipoproteins E - genetics
AST-120
Blood Pressure
Carbon - administration & dosage
Cardiovascular
Cardiovascular Diseases - complications
Cardiovascular Diseases - drug therapy
Cell Survival
CKD
Echocardiography
Endothelial dysfunction
Endothelium, Vascular - pathology
Female
Human Umbilical Vein Endothelial Cells
Humans
Indican - adverse effects
Indican - chemistry
Indoxyl sulfate
Intercellular Adhesion Molecule-1 - metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mouse
Oxides - administration & dosage
Pulse Wave Analysis
Renal Insufficiency, Chronic - complications
Renal Insufficiency, Chronic - drug therapy
Uremia - metabolism
Vascular Cell Adhesion Molecule-1 - metabolism
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Summary:Abstract Background In chronic kidney disease (CKD), blood vessels are permanently exposed to uremic toxins such as indoxyl sulfate (IS). We hypothesized that IS could alter vascular tone and that reducing its serum concentration could be beneficial. Design We studied acute and longer-term effects of IS and AST-120, an oral charcoal adsorbent, on vascular reactivity, endothelium integrity and expression of adhesion molecules VCAM-1 and ICAM-1 in aortic rings of normal and uremic wild type (WT) mice in vitro , and the cardiovascular effects of AST-120 in both WT and apoE−/− mice with CKD in vivo. Results In vitro , 1.0 mM IS acutely reduced vascular relaxation (64% for IS 1.0 mM vs. 80% for control, p 
ISSN:0021-9150
1879-1484
DOI:10.1016/j.atherosclerosis.2015.09.019