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Atherosclerosis and Metabolism Unit
Department of Molecular and Cardiovascular Research
Katholieke Universiteit Leuven
Herestraat 49, PB 705
B-3000 Leuven
Belgium
E-mail: paul.holvoet{at}med.kuleuven.be
Dear Sir:
I read with great interest the article by Weinbrenner et al (1) on the association between waist circumference and circulating oxidized LDL and the editorial by Knopp and Paramsothy (2).
Knopp and Paramsothy concluded that the study by Weinbrenner et al showed an increase in immunologically detected epitopes of lipid peroxides in the LDLs of persons with abdominal obesity. However, Weinbrenner et al measured circulating concentrations of oxidized LDL with an enzyme-linked immunosorbent assay procedure that uses the monoclonal antibody 4E6 (Mercodia AB, Uppsala, Sweden). Because this antibody was developed in my laboratory (3), I would like to correctly describe the characteristics of this monoclonal antibody. It is directed against a conformational epitope in the apolipoprotein B-100 moiety of LDL that is generated as a consequence of the substitution of 60 lysine residues of apolipoprotein B-100 with aldehydes. This number of substituted lysines corresponds to the minimum number required for scavenger-mediated uptake of oxidized LDL. Substituting aldehydes can be produced by peroxidation of lipids of LDL, which results in the generation of oxidized LDL. However, lipid peroxidation is not required. Indeed, aldehydes that are released by endothelial cells under oxidative stress or by activated platelets may also induce the oxidative modification of apolipoprotein B-100 in the absence of peroxidation of lipids of LDL.
In their editorial, Knopp and Paramsothy refer to the study by Ford et al (4), which showed indirect evidence that oxidative stress is enhanced in the metabolic syndrome. They reported reduced concentrations of antioxidant vitamins in association with the metabolic syndrome in the third National Health and Nutrition Examination Survey (NHANES III) cohort. Although the authors did not refer to our previous publication, we would like to draw their attention to our study of the association between the metabolic syndrome and circulating oxidized LDL in the Health, Aging, and Body Composition (Health ABC) cohort. This cohort appeared to be representative of the US population. The prevalence of the metabolic syndrome as defined by the Adult Treatment Panel III (3 or more components) in the Health ABC cohort was 38% (1147 participants with the metabolic syndrome) compared with 42% in a similar-aged population in NHANES III. In addition, the prevalence of diabetes, smoking, and hypertension; mean BMI; mean waist circumference; and mean LDL-cholesterol, HDL-cholesterol, and triacylglycerol concentrations was similar between the 2 study populations. We observed that the metabolic syndrome was associated with higher concentrations of oxidized LDL, because of a higher fraction of oxidized LDL, and not to higher concentrations of LDL cholesterol. The odds of persons with the metabolic syndrome having high oxidized LDL (>1.90 mg/dL) concentrations was twice that of those not having the metabolic syndrome after adjustment for age, sex, ethnicity, smoking status, and LDL cholesterol. In those participants who had the metabolic syndrome at study entry, the incidence of future cardiovascular disease events was 1.6-fold higher after adjustment for age, sex, ethnicity, and smoking status. Oxidized LDL was not an independent predictor of total cardiovascular disease risk. However, those with high oxidized LDL concentrations had a greater disposition to myocardial infarction (adjusted relative risk: 2.25; 95% CI: 1.22, 4.15). We concluded that the metabolic syndrome, a risk factor for cardiovascular disease, is associated with higher concentrations of circulating oxidized LDL, which are associated with a greater disposition to atherothrombotic coronary disease (5).
Although I do not question the merits of the study by Weinbrenner et al or the valuable comments of Knopp and Paramsothy, I wanted to put some of the data in perspective.
ACKNOWLEDGMENTS
The author had no conflict of interest related to this letter.
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