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- Nordin Fredrikson, Gunilla, et al.
(författare)
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Association between IgM against an aldehyde-modified peptide in apolipoprotein B-100 and progression of carotid disease
- 2007
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 38:5, s. 1495-1500
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose - Autoantibodies against antigens in oxidized low-density lipoprotein are common in people; experimental studies suggest that these immune responses have a functional role in the disease process. The aim of this study was to evaluate the relationship between the immune response against one defined oxidized low-density lipoprotein antigen, the aldehyde-modified peptide corresponding amino acids 3136 and 3155 (MDA-p210) in apolipoprotein (apo) B-100, and progression of carotid intima media thickness (IMT). Methods - IgM and IgG against MDA-p210 were determined by enzyme-linked immunosorbent assay at baseline and after 12 months of treatment with placebo, metoprolol, fluvastatin, or metoprolol/ fluvastatin in 751 individuals participating in the BCAPS. Carotid IMT was assessed by ultrasonography at baseline and after 18 and 36 months of treatment. Results - Antibody levels did not change in response to treatment, but high baseline MDA-p210 IgM levels were associated with a more rapid progression of carotid disease both at 18 ( r = 0.09, P < 0.05) and 36 months ( r = 0.12, P < 0.005). At 36 months, the difference in IMT progression rate per year between those with high MDA-p210 IgM levels and those with low was 0.011 mm ( 95% CI = 0.005 to 0.018 mm, P < 0.0001). Treatment with fluvastatin markedly decreased the progression of IMT among subjects with high but not with low MDA-p210 IgM levels. There was no association between MDA-p210 IgG and carotid IMT progression. Conclusions - IgM against the aldehyde-modified peptide corresponding amino acids 3136 and 3155 in apo B-100 is common in subjects with asymptomatic carotid disease, and high levels are associated with a more rapid progression of carotid IMT. The observation that the effect of fluvastatin was restricted to subjects with high MDA-p210 IgM levels may reflect the increased rate of disease progression in this group.
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- Nordin Fredrikson, Gunilla, et al.
(författare)
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Identification of autoantibodies in human plasma recognizing an apoB-100 LDL receptor binding site peptide
- 2006
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Ingår i: Journal of Lipid Research. - 1539-7262 .- 0022-2275. ; 47:9, s. 2049-2054
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to test the hypothesis that autoantibodies recognize amino acid sequences in the LDL receptor binding region of apolipoprotein B-100 (apoB-100). Autoantibodies against an unmodified or malondialdehyde (MDA)-modified LDL receptor binding site peptide were determined by ELISA in baseline plasma samples of 78 cases with coronary events and 149 matched controls recruited from the prospective Malmo Diet Cancer Study. IgG and IgM recognizing this peptide were detected in all subjects but did not differ between cases and controls. Inverse associations were observed between IgG against the native binding site and plasma oxidized LDL (r = -0.21, P < 0.005), but there were no significant associations with total or LDL cholesterol levels. In univariate analyses, inverse associations were found between baseline carotid intima-media thickness and IgG against the MDA-modified binding site (r = -0.14, P < 0.05), but this association was lost when controlling for other major cardiovascular risk factors. Specificity studies demonstrated that the binding of autoantibodies to these sequences could be inhibited by oxidized but not by native LDL. Autoantibodies recognizing the LDL receptor binding site in apoB-100 are frequently expressed. Their association with plasma oxidized LDL suggests that they have been generated in response to breakdown products of LDL oxidation, but their influence on cholesterol metabolism and the development of atherosclerosis appears limited.
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