Effect of AST-120 on Endothelial Dysfunction in Adenine-Induced Uremic Rats.
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- β 1 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.
Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Yuko
Y
Inami
Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Chieko
C
Hamada
Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Takuya
T
Seto
Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Yoko
Y
Hotta
Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Seiki
S
Aruga
Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Jiro
J
Inuma
Division of Metabolism and Endocrinology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, Tokyo, Japan.
Kosuke
K
Azuma
Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Hiroaki
0000-0002-9446-2390
H
Io
Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Kayo
K
Kaneko
Division of Metabolism and Endocrinology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, Tokyo, Japan.
Hirotaka
H
Watada
Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Yasuhiko
0000-0003-2689-3620
Y
Tomino