TY - JOUR
T1 - Low-density lipoprotein apheresis for haemodialysis patients with peripheral arterial disease reduces reactive oxygen species production via suppression of NADPH oxidase gene expression in leucocytes
AU - Hara, Taiga
AU - Kiyomoto, Hideyasu
AU - Hitomi, Hirofumi
AU - Moriwaki, Kumiko
AU - Ihara, Genei
AU - Kaifu, Kumiko
AU - Fujita, Yoshiko
AU - Higashiyama, Chikako
AU - Nishiyama, Akira
AU - Kohno, Masakazu
N1 - Funding Information:
Acknowledgements. The authors thank Dr Yasuo Kaifu, Dr Taku Oota and Dr Yasunori Iwasaki who participated in this study. This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (17590830 and 2159105 to H.K.) and partially by a grant from Sanju alumni Research Grant.
PY - 2009/12
Y1 - 2009/12
N2 - Background. Peripheral arterial disease (PAD) is a major complication of haemodialysis (HD), especially in patients with diabetes mellitus. Although previous reports have indicated that low-density lipoprotein apheresis (LDL-A) improves arteriosclerosis in PAD patients, the mechanism by which LDL-A affects PAD is still unclear. In this study, we tested the hypothesis that LDL-A attenuates reactive oxygen species (ROS) production in HD patients with PAD.Methods. Twenty HD patients with PAD were investigated in this study. Clinical effects were evaluated by thermography and angiography. Oxidative stress in serum was evaluated by thiobarbituric acid reactive substances (TBARS) and expression of p22phox mRNA.Results. Ischaemic symptoms due to PAD were gradually improved in 13 patients (65) after LDL-A. One session of LDL-A removed ∼75 of LDL from serum. Some patients exhibited dramatic improvement of severe symptoms of PAD such as skin ulcers after serial performance of LDL-A. The levels of LDL cholesterol, malondialdehyde-modified LDL, high-sensitivity C-reactive protein, vascular endothelial growth factor, international normalized ratio of pro-thrombin time and bradykinin were decreased after a single session of LDL-A, although there were no additional changes after 10 sessions of LDL-A. The levels of fibrinogen and p22phox mRNA were decreased by a single session of LDL-A, and these decreases continued over the entire period of treatment. TBARS was decreased after a course of LDL-A.Conclusions. LDL-A improved ischaemic symptoms in HD patients with PAD by reducing ROS production in leucocytes. We conclude that LDL-A is an effective therapy for patients with HD complicated by PAD.
AB - Background. Peripheral arterial disease (PAD) is a major complication of haemodialysis (HD), especially in patients with diabetes mellitus. Although previous reports have indicated that low-density lipoprotein apheresis (LDL-A) improves arteriosclerosis in PAD patients, the mechanism by which LDL-A affects PAD is still unclear. In this study, we tested the hypothesis that LDL-A attenuates reactive oxygen species (ROS) production in HD patients with PAD.Methods. Twenty HD patients with PAD were investigated in this study. Clinical effects were evaluated by thermography and angiography. Oxidative stress in serum was evaluated by thiobarbituric acid reactive substances (TBARS) and expression of p22phox mRNA.Results. Ischaemic symptoms due to PAD were gradually improved in 13 patients (65) after LDL-A. One session of LDL-A removed ∼75 of LDL from serum. Some patients exhibited dramatic improvement of severe symptoms of PAD such as skin ulcers after serial performance of LDL-A. The levels of LDL cholesterol, malondialdehyde-modified LDL, high-sensitivity C-reactive protein, vascular endothelial growth factor, international normalized ratio of pro-thrombin time and bradykinin were decreased after a single session of LDL-A, although there were no additional changes after 10 sessions of LDL-A. The levels of fibrinogen and p22phox mRNA were decreased by a single session of LDL-A, and these decreases continued over the entire period of treatment. TBARS was decreased after a course of LDL-A.Conclusions. LDL-A improved ischaemic symptoms in HD patients with PAD by reducing ROS production in leucocytes. We conclude that LDL-A is an effective therapy for patients with HD complicated by PAD.
KW - C-reactive protein (CRP)
KW - NADPH oxidase
KW - Oxidative stress
KW - P22phox
KW - Thiobarbituric acid reactive substance (TBARS)
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U2 - 10.1093/ndt/gfp342
DO - 10.1093/ndt/gfp342
M3 - Article
C2 - 19617260
AN - SCOPUS:71049141220
VL - 24
SP - 3818
EP - 3825
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
SN - 0931-0509
IS - 12
ER -