Effect of AST-120 on Endothelial Dysfunction in Adenine-Induced Uremic Rats

Abstract EN

Aim.

Chronic kidney disease (CKD) represents endothelial dysfunction.

Monocyte adhesion is recognized as the initial step of arteriosclerosis.

Indoxyl sulfate (IS) is considered to be a risk factor for arteriosclerosis in CKD.

Oral adsorbent AST-120 retards deterioration of renal function, reducing accumulation of IS.

In the present study, we determined the monocyte adhesion in the adenine-induced uremic rats in vivo and effects of AST-120 on the adhesion molecules.

Methods.

Twenty-four rats were divided into control, control+AST-120, adenine, and adenine+AST-120 groups.

The number of monocytes adherent to the endothelium of thoracic aorta by imaging the entire endothelial surface and the mRNA expressions of adhesion and atherosclerosis-related molecules were examined on day 49.

The mRNA expressions of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells were also examined.

Results.

Adenine increased the number of adherent monocytes, and AST-120 suppressed the increase.

The monocyte adhesion was related to serum creatinine and IS in sera.

Overexpression of VCAM-1 and TGF-β1 mRNA in the arterial walls was observed in uremic rats.

IS induced increase of the ICAM-1 and VCAM-1 mRNA expressions in vitro.

Conclusion.

It appears that uremic condition introduces the monocyte adhesion to arterial wall and AST-120 might inhibit increasing of the monocyte adherence with CKD progression.