Oxidized Phospholipids Are Present on Plasminogen, Affect Fibrinolysis, and Increase Following Acute Myocardial Infarction

Leibundgut, Gregor; Arai, Kiyohito; Orsoni, Alexina; Yin, Huiyong; Scipione, Corey A.; Miller, Elizabeth R.; Koschinsky, Marlys L.; Chapman, M. John; Witztum, Joseph L.; Tsimikas, Sotirios

doi:10.1016/j.jacc.2011.12.033

Cited by 64 publications

(62 citation statements)

References 38 publications

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“…Further work removing the entire KIV 10 and/or utilizing site-specifi c mutagenesis of likely immunoreactivity, a fi nding that seems to be explained by their KIV 10 Asp 57 → Ala 57 substitution compared with human apo(a). This observation does not appear to be due to lack of circulating OxPLs, as cholesterol-and fat-fed cynomolgus monkeys with total plasma cholesterol ‫ف‬ 700 mg/dl and abundant E06-detectable OxPLs in atherosclerotic lesions also do not have E06-detectable OxPLs on Lp(a), as shown previously ( 34 ), but they do on PLG which has an intact KIV 10 LBS compared with Lp(a) ( 25 ). In addition, cynomolgus monkeys do carry OxPLs on apoB particles, as previously shown ( 34 ).…”

Section: Discussionsupporting

confidence: 77%

“…LC-MS/MS analysis was carried out on a triple quadrupole instrument Thermal TSQ Vantage mass spectrometer coupled with a Waters NanoAcquity autosampler/UPLC system, as previously described ( 25,37 ). The LC separation was achieved on a trapping column with 5 cm of 5 m Jupiter C18 reverse phase material pressure-packed into a fused silica capillary (360 m o.d.…”

Section: Resultsmentioning

confidence: 99%

“…More recently, we also demonstrated that PLG of a variety of species contains covalently bound OxPLs ( 25 ). In contrast to the pro-atherogenic effects of OxPLs on Lp(a), OxPLs on PLG promote fi brinolysis, whereas the absence of OxPLs on PLG result in delayed fi brinolysis, which would be predicted to be atheroprotective ( 25 ).…”

mentioning

confidence: 85%

“…In contrast to the pro-atherogenic effects of OxPLs on Lp(a), OxPLs on PLG promote fi brinolysis, whereas the absence of OxPLs on PLG result in delayed fi brinolysis, which would be predicted to be atheroprotective ( 25 ).…”

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confidence: 97%

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Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)

Leibundgut

Scipione

Yin

et al. 2013

Journal of Lipid Research

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185

146

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Section: Discussionsupporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 85%

mentioning

confidence: 97%

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Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)

Leibundgut

Scipione

Yin

et al. 2013

Journal of Lipid Research

Self Cite

185

146

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“…A similar result is observed with E06, which recognizes the phosphocholine head-group of oxidized phospholipids that are present in oxidized LDL and BSA-conjugated PC (29,61). Nevertheless, when E06 is used for Western blot analysis, the antibody recognizes a band of oxidized LDL without highlighting other PC-modified proteins (80).…”

Section: Discussionmentioning

confidence: 99%

Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody

Frescas

Roux

Aygun‐Sunar

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

113

103

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Studying the phenomenon of cellular senescence has been hindered by the lack of senescence-specific markers. As such, detection of proteins informally associated with senescence accompanies the use of senescence-associated β-galactosidase as a collection of semiselective markers to monitor the presence of senescent cells. To identify novel biomarkers of senescence, we immunized BALB/c mice with senescent mouse lung fibroblasts and screened for antibodies that recognized senescence-associated cell-surface antigens by FACS analysis and a newly developed cell-based ELISA. The majority of antibodies that we isolated, cloned, and sequenced belonged to the IgM isotype of the innate immune system. In-depth characterization of one of these monoclonal, polyreactive natural antibodies, the IgM clone 9H4, revealed its ability to recognize the intermediate filament vimentin. By using 9H4, we observed that senescent primary human fibroblasts express vimentin on their cell surface, and MS analysis revealed a posttranslational modification on cysteine 328 (C328) by the oxidative adduct malondialdehyde (MDA). Moreover, elevated levels of secreted MDA-modified vimentin were detected in the plasma of aged senescence-accelerated mouse prone 8 mice, which are known to have deregulated reactive oxygen species metabolism and accelerated aging. Based on these findings, we hypothesize that humoral innate immunity may recognize senescent cells by the presence of membrane-bound MDA-vimentin, presumably as part of a senescence eradication mechanism that may become impaired with age and result in senescent cell accumulation.aging | oxidative posttranslational modifications | biomarker | SAMP8 | malondialdehyde

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Oxidized phospholipids and lipoprotein‐associated phospholipase A₂ (Lp‐PLA₂) in atherosclerotic cardiovascular disease: An update

2022

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Inflammation and oxidative stress conditions lead to a variety of oxidative modifications of lipoprotein phospholipids implicated in the occurrence and development of atherosclerotic lesions. Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) is established as an independent risk biomarker of atherosclerosis-related cardiovascular disease (ASCVD) and mediates vascular inflammation through the regulation of lipid metabolism in the blood and in atherosclerotic lesions. Lp-PLA 2 is associated with low-and high-density lipoproteins and Lipoprotein (a) in human plasma and specifically hydrolyzes oxidized phospholipids involved in oxidative stress modification. Several oxidized phospholipids (OxPLs) subspecies can be detoxified through enzymatic degradation by Lp-PLA 2 activation, forming lysophospholipids and oxidized nonesterified fatty acids (OxNEFAs). Lysophospholipids promote the expression of adhesion molecules, stimulate cytokines production (TNF-α, IL-6), and attract macrophages to the arterial intima. The present review article discusses new data on the functional roles of OxPLs and Lp-PLA 2 associated with lipoproteins.

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Oxidized Phospholipids Are Present on Plasminogen, Affect Fibrinolysis, and Increase Following Acute Myocardial Infarction

Cited by 64 publications

References 38 publications

Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)

Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)

Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody

Oxidized phospholipids and lipoprotein‐associated phospholipase A₂ (Lp‐PLA₂) in atherosclerotic cardiovascular disease: An update

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Oxidized Phospholipids Are Present on Plasminogen, Affect Fibrinolysis, and Increase Following Acute Myocardial Infarction

Cited by 64 publications

References 38 publications

Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)

Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)

Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody

Oxidized phospholipids and lipoprotein‐associated phospholipase A2 (Lp‐PLA2) in atherosclerotic cardiovascular disease: An update

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Oxidized phospholipids and lipoprotein‐associated phospholipase A₂ (Lp‐PLA₂) in atherosclerotic cardiovascular disease: An update