Possible involvement of increased glycoxidation and lipid peroxidation of elastin in atherogenesis in haemodialysis patients.
BACKGROUND
Glycoxidation and lipid peroxidation products accumulate in collagen of various tissues in haemodialysis patients with end-stage renal disease (ESRD). The purpose of this study was to test the hypothesis that increased glycoxidation and lipid peroxidation of aortic elastin is implicated in the cardiovascular complications, particularly atherosclerosis, of chronic haemodialysis patients.


METHODS
Post-mortem aortic samples were obtained from 16 deceased subjects, including chronic haemodialysis patients (group 1 n=6, age 64.7+/-11.4 years) and control subjects (group 2 n=10, age 61.1+/-10.4 years). The samples were divided into three vessel wall sites: atherosclerotic intima, lesion-free intima, and media. They were sequentially treated with 0.01 M phosphate-buffered saline, collagenase, and elastase to obtain three fractions, namely soluble (SF), collagen (CF), and elastin (EF) fractions, respectively. Using spectrophotofluorometry, the pentosidine- and malondialdehyde (MDA)-linked fluorescence of these fractions was measured at wavelengths 335/385 and 390/460 (excitation/emission), respectively.


RESULTS
Samples from haemodialysis patients (group 1) exhibited a significant increase in both pentosidine- and MDA-linked fluorescence of EF in atherosclerotic intima, lesion-free intima, and media samples, compared with samples from control subjects (group 2). In group 1, the levels of pentosidine- and MDA-linked fluorescence of EF were highest in atherosclerotic intima among the three aortic sites. Interestingly, in both groups, the levels of pentosidine- and MDA-linked fluorescence of EF were significantly higher than those of CF in all aortic sites. There was a strong correlation between the levels of pentosidine- and MDA-linked fluorescence in CF and EF for all aortic sites. In group 1, the pentosidine- and MDA-linked fluorescence levels of EF correlated significantly with the duration of haemodialysis in lesion-free intima and media.


CONCLUSIONS
Our study provides the first biochemical evidence for a close link between aortic elastin glycoxidation and lipid peroxidation. In addition, we demonstrated high levels of these products in the aortic elastin of haemodialysis patients with ESRD. Our findings support the hypothesis that modification of aortic elastin by glycoxidation and lipid peroxidation may contribute to the development of vascular complications, particularly atherosclerosis, in patients with end-stage renal failure.
Yamamoto
Yuji
Y
Second Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan.
Sakata
Noriyuki
N
Meng
Jing
J
Sakamoto
Masaya
M
Noma
Akiko
A
Maeda
Iori
I
Okamoto
Kouji
K
Takebayashi
Shigeo
S
D001161:Arteriosclerosis / Q000209:etiology*; D002097:C-Reactive Protein / Q000032:analysis; D004549:Elastin / Q000378:metabolism*; D005453:Fluorescence; D006031:Glycosylation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000032:analysis; D010084:Oxidation-Reduction; D006435:Renal Dialysis / Q000009:adverse effects*
D008315:Malondialdehyde; D002097:C-Reactive Protein; D004549:Elastin