Sustained inhibition of oxidized low-density lipoprotein is involved in the long-term therapeutic effects of apheresis in dialysis patients.
OBJECTIVE
Low-density lipoprotein (LDL) apheresis is a potential therapy for conventional therapy-resistant peripheral artery disease. In the present study, we examined the chronic effects of LDL apheresis on clinical parameters in vivo and endothelial cell functions in vitro in hemodialysis patients who had the complication of peripheral artery disease.


RESULTS
Twenty-five patients were enrolled, and the responses of 19 patients to LDL apheresis were analyzed. Patients were classified into 2 groups according to change in ankle-brachial pressure index (ABI) after treatment: patients with improved ABI (responders, n=10) and patients with worsened ABI (nonresponders, n=9). In the responders, apheresis resulted in a long-term reduction of circulating levels of oxidized LDL, C-reactive protein, and fibrinogen. In human umbilical vein endothelial cells (HUVECs), the serum from the responders increased expression of activated endothelial nitric oxide synthase protein and proliferative activity. Furthermore, there was a significant correlation between ABI and activated endothelial nitric oxide synthase protein level in HUVECs treated with responder serum (R=0.427, P<0.05).


CONCLUSIONS
These results demonstrate that LDL apheresis decreases oxidized LDL and inflammation and improves endothelial cell function in the responders. This may be one of the mechanisms involved in the long-term therapeutic effect of LDL apheresis on peripheral circulation in hemodialysis patients.
Tsurumi-Ikeya
Yuko
Y
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Tamura
Kouichi
K
Azuma
Koichi
K
Mitsuhashi
Hiroshi
H
Wakui
Hiromichi
H
Nakazawa
Ichiro
I
Sugano
Teruyasu
T
Mochida
Yasuyuki
Y
Ebina
Toshiaki
T
Hirawa
Nobuhito
N
Toya
Yoshiyuki
Y
Uchino
Kazuaki
K
Umemura
Satoshi
S
D000368:Aged; D055109:Ankle Brachial Index; D015415:Biomarkers / Q000097:blood; D001781:Blood Component Removal; D002097:C-Reactive Protein / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000628:therapy; D007674:Kidney Diseases / Q000150:complications / Q000628:therapy*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D020127:Recovery of Function; D006435:Renal Dialysis; D013997:Time Factors; D016896:Treatment Outcome; D016138:Walking
D015415:Biomarkers; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D005340:Fibrinogen; D002097:C-Reactive Protein; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III