Dataset Information

Indoxyl sulfate and p-cresyl sulfate directly promote vascular calcification via activation of inflammation and coagulation pathways

ABSTRACT: Vascular calcification contributes to high cardiovascular mortality in chronic kidney disease (CKD) patients. An association between the uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS) and cardiovascular disease has been suggested. This study provides strong etiological evidence for indoxyl sulfate and p-cresyl sulfate as major contributors to vascular calcification in chronic kidney disease patients. Continuous exposure to indoxyl sulfate or p-cresyl sulfate in rats with chronic kidney disease promotes moderate to severe calcification in the aorta and peripheral vessels. Unbiased proteomic analyses of arterial samples coupled to functional bioinformatics annotation analysis revealed that calcification events were associated with acute phase response signaling, coagulation and glucometabolic signaling pathways, while escape from toxin-induced calcification was linked with liver X receptors and farnesoid X/liver X receptor signaling pathways. Activation of inflammation and coagulation pathways in the arterial wall plays a pivotal role in toxin-induced calcification and strongly associates with hyperglycemia and insulin resistance. These findings reveal new perspectives to establish novel therapeutic targets to prevent, halt progression or cure vascular calcification.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Aorta

DISEASE(S): Chronic Kidney Disease

SUBMITTER: Abdelkrim Azmi

LAB HEAD: Patrick C. D’Haese

PROVIDER: PXD012582 | Pride | 2019-06-13

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	AortaRat8plexISPCS301018plex1_01.raw	Raw
	AortaRat8plexISPCS301018plex1_02.raw	Raw
	AortaRat8plexISPCS301018plex1_03.raw	Raw
	AortaRat8plexISPCS301018plex1_04.raw	Raw
	AortaRat8plexISPCS301018plex1_05.raw	Raw

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Publications

Indoxyl Sulfate and p-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose Intolerance.

Opdebeeck Britt B Maudsley Stuart S Azmi Abdelkrim A De Maré Annelies A De Leger Wout W Meijers Bjorn B Verhulst Anja A Evenepoel Pieter P D'Haese Patrick C PC Neven Ellen E

Journal of the American Society of Nephrology : JASN 20190402 5

<h4>Background</h4>Protein-bound uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS) have been associated with cardiovascular morbidity and mortality in patients with CKD. However, direct evidence for a role of these toxins in CKD-related vascular calcification has not been reported.<h4>Methods</h4>To study early and late vascular alterations by toxin exposure, we exposed CKD rats to vehicle, IS (150 mg/kg per day), or PCS (150 mg/kg per day) for either 4 days (short-term exposure) or ...[more]

PMID: 30940651

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