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Atherosclerosis and Lipoproteins |
From the Department of Clinical Cell Biology (K. Tanaga, K. Takahashi, Y.S.), F5, and the Department of Genome Research and Clinical Application (H.B.), M6, Chiba University Graduate School of Medicine, Chiba; Omigawa Hospital (M.I., K.M.), Omigawa; Daiichi Pure Chemicals (K.K.), Tokyo; and Hamamatsu University School of Medicine (T.K.), Hamamatsu, Japan.
Correspondence to Dr Hideaki Bujo, Department of Genome Research and Clinical Application (M6), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail hbujo{at}intmed02.m.chiba-u.ac.jp
Recent establishment of a sensitive ELISA system using antibodies against malondialdehyde-modified low density lipoprotein (MDA-LDL) made it possible to determine the circulating oxidized lipoprotein levels. Here, we investigated the serum levels of MDA-LDL in 62 patients with coronary artery disease (CAD) compared with the levels in 42 patients without CAD [groups CAD(+) and CAD(-), respectively], which are adjusted for age, serum total cholesterol, LDL and high density lipoprotein cholesterol, and triglyceride levels. Serum MDA-LDL levels were 113.4±49.1 IU/L in CAD(+), which were significantly higher than the levels in CAD(-) (85.2±22.5 IU/L, P<0.0005). The ratio of MDA-LDL/LDL cholesterol was 0.95±0.32 in CAD(+), indicating a significant increase compared with the ratio in CAD(-) (0.68±0.19, P<0.0005). The positive correlation of MDA-LDL level and the ratio of MDA-LDL/LDL cholesterol with intima-media thickness in carotid arteries was observed. Age was not clearly associated with the MDA-LDL level (P=0.865). The serum MDA level was positively correlated with LDL cholesterol (P<0.0001) and with triglycerides (P<0.001) and negatively correlated with high density lipoprotein cholesterol (P<0.05). Furthermore, the MDA-LDL level was negatively correlated with the peak size of the LDL particle (P<0.01). The LDL subclasses that were identified by using the sera collected from the subjects by sequential ultracentrifugation showed that the ratios of MDA-LDL/apolipoprotein B in LDL3 and LDL4 were nearly 3-fold higher than those in LDL1 and LDL2 for CAD(+) and CAD(-). These results indicate that the circulating MDA-LDL level is increased in CAD(+), independent of the serum LDL cholesterol level but in association with the peak size of LDL particles. The measurement of serum MDA-LDL level may be useful for the identification of patients with advanced atherosclerosis.
Key Words: malondialdehyde-modified LDL coronary artery disease ELISA atherosclerosis
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