Lysophosphatidylcholine Is Involved in the Antigenicity of Oxidized LDL

Wu, Ruihua; Huang, Yui Hui; Elinder, Liselotte Schäfer; Frostegård, Johan

doi:10.1161/01.atv.18.4.626

Cited by 71 publications

(57 citation statements)

References 31 publications

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“…These antibodies are detected using cardiolipin [89] or commercial preparations of PC complexed with bovine serum albumin [81], and the reaction of patient's sera with this substrate cab be inhibited by oxLDL. The phospholipid antibodies detected by these methods seem to be predominantly of the IgM isotype [81,89] and it has been postulated that they recognize PC epitopes shared by Streptococcus pneumoniae. Mice immunized with Streptococcus pneumoniae produce antibodies (predominantly of the IgM isotype) that appear to cross-react with PC in oxLDL [75,77].…”

Section: The Role Of Phospholipid Antibodies In Atherosclerosismentioning

confidence: 99%

Atherogenesis and the humoral immune response to modified lipoproteins

Virella¹,

Lopes‐Virella²

2008

Atherosclerosis

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Modified forms of LDL are immunogenic and activate both cell-mediated and humoral immune responses. Both types of responses are pro-inflammatory and are probably primary players in the perpetuation of the chronic inflammatory reaction characteristic of atherosclerosis. The immunologic response to modified LDL can be directed to MHC-II-associated peptides in the case of T helper cells, and to a variety of epitopes -modified lysine groups, modified phospholipids, proteins that become associated with oxidized LDL (such as β2GP1) -in the case of B cell responses. T cell activation is likely to play a major role through cross-activation of macrophages. Humoral responses to modified LDL are pathogenic as a consequence of the formation of antigen-antibody complexes containing modified LDL and IgG antibodies. Those immune complexes induce cholesterol ester accumulation in macrophages and macrophage-like cells, and induce the release of proinflammatory cytokines, chemokines, oxygen active radicals, and matrix metalloproteinases from those cells. There is no conclusive evidence supporting a protective role for IgM antibodies in humans, possibly because autoantibodies to modified lipoproteins are predominantly of the IgG isotype.

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Section: The Role Of Phospholipid Antibodies In Atherosclerosismentioning

confidence: 99%

Atherogenesis and the humoral immune response to modified lipoproteins

Virella¹,

Lopes‐Virella²

2008

Atherosclerosis

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“…Once lymphocytes are recruited into the developing plaque, lysoPC may complex with peptides and serve as antigen to stimulate T cells. 57 On T-cell activation, the immune reactions within the vessel wall are not only sustained but enhanced. As the plaque progresses, lysoPC may promote vascular SMC proliferation by activating DNA synthesis.…”

Section: Szmitko Et Al Inflammation and Endothelial Cell Activation 2043mentioning

confidence: 99%

Biomarkers of Vascular Disease Linking Inflammation to Endothelial Activation

et al. 2003

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A therosclerosis is regarded as a dynamic and progressive disease arising from the combination of endothelial dysfunction and inflammation. [1][2][3][4][5][6] This article is the second in a 2-part series examining emerging markers of inflammation and endothelial cell activation. The first article 7 provided a brief overview of the link between inflammation, endothelial dysfunction, and atherosclerosis and began the examination of emerging inflammatory mediators. This second article continues with an exploration of more novel markers for cardiovascular disease.

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“…This lysophospholipid product of Lp-PLA # action has been shown, for example, to be capable of promoting monocyte recruitment either directly by functioning as a chemoattractant itself [16] or indirectly via the selective induction of endothelial leucocyte adhesion molecules [17,18]. Lyso-PtdCho has also been identified as the component of oxidized LDL that promotes both smooth muscle [19] and macrophage [20] proliferation, induces endothelial dysfunction in various arteries [6,21] and is involved in the antigenicity of oxidized LDL [22]. There has been considerable discussion over whether Lp-PLA # primarily has a pro-inflammatory (generation of lyso-PtdCho) or anti-inflammatory (degradation of PAF or PAF-like lipids) role in atherogenesis [15,23,24].…”

mentioning

confidence: 99%

Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor

Macphee

Moores

Boyd

et al. 1999

Biochemical Journal

262

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A novel and potent azetidinone inhibitor of the lipoprotein-associated phospholipase A2 (Lp-PLA2), i.e. platelet-activating factor acetylhydrolase, is described for the first time. This inhibitor, SB-222657 (Ki = 40±3 nM, kobs/[I] = 6.6×105 M-1·s-1), is inactive against paraoxonase, is a poor inhibitor of lecithin:cholesterol acyltransferase and has been used to investigate the role of Lp-PLA2 in the oxidative modification of lipoproteins. Although pretreatment with SB-222657 did not affect the kinetics of low-density lipoprotein (LDL) oxidation by Cu2+ or an azo free-radical generator as determined by assay of lipid hydroperoxides (LOOHs), conjugated dienes and thiobarbituric acid-reacting substances, in both cases it inhibited the elevation in lysophosphatidylcholine content. Moreover, the significantly increased monocyte chemoattractant activity found in a non-esterified fatty acid fraction from LDL oxidized by Cu2+ was also prevented by pretreatment with SB-222657, with an IC50 value of 5.0±0.4 nM. The less potent diastereoisomer of SB-222657, SB-223777 (Ki = 6.3±0.5 µM, kobs/[I] = 1.6×104 M-1·s-1), was found to be significantly less active in both assays. Thus, in addition to generating lysophosphatidylcholine, a known biologically active lipid, these results demonstrate that Lp-PLA2 is capable of generating oxidized non-esterified fatty acid moieties that are also bioactive. These findings are consistent with our proposal that Lp-PLA2 has a predominantly pro-inflammatory role in atherogenesis. Finally, similar studies have demonstrated that a different situation exists during the oxidation of high-density lipoprotein, with enzyme(s) other than Lp-PLA2 apparently being responsible for generating lysophosphatidylcholine.

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Lysophosphatidylcholine Is Involved in the Antigenicity of Oxidized LDL

Cited by 71 publications

References 31 publications

Atherogenesis and the humoral immune response to modified lipoproteins

Atherogenesis and the humoral immune response to modified lipoproteins

Biomarkers of Vascular Disease Linking Inflammation to Endothelial Activation

Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor

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