Percutaneous Coronary Intervention Results in Acute Increases in Oxidized Phospholipids and Lipoprotein(a)

Tsimikas, Sotirios; Lau, Hung; Han, Kyoo‐Rok; Shortal, Brian; Miller, Elizabeth R.; Segev, Amit; Curtiss, Linda K.; Witztum, Joseph L.; Strauss, Bradley H.

doi:10.1161/01.cir.0000130844.01174.55

Cited by 233 publications

(222 citation statements)

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“…The above results are also supported by the studies about ox-PL, which have demonstrated convincingly that a key ox-PL is preferentially associated with Lp(a) [52] and correlates with both the presence and extent of angiographically documented CAD [40,53], and their concentrations increase after ACS [51] and immediately after PCI [54].…”

Section: The Clinical Value Of Circulating Oxidized Lp(a)supporting

confidence: 63%

Lipoprotein(a) Oxidation, Autoimmune and Atherosclerosis

Wang¹

2012

Coronary Artery Disease - New Insights and Novel Approaches

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IntroductionLipoprotein(a) [Lp(a)] is a plasma lipoprotein whose structure and composition closely resembles that of low density lipoprotein (LDL), but with one of additional molecule of apolipoprotein(a) [apo(a)], a large glycoprotein linked to apoB by a disulfide bond (Figure 1) [1,2]. High Lp(a) levels have been established as an independent risk factor for atherocslerosis [3][4][5], and Lp(a) deposits have been found in atherosclerotic lesions but not in normal arterial walls [6][7][8].Lp(a) can be modified by oxidation in vitro, and then be taken up by macrophages by means of scavenger receptors, where it promotes their transformation into foam cells within the arterial walls [9][10][11][12][13]. Oxidized Lp(a) [ox-Lp(a)] may also induce adhesion molecular expression on monocytes, promoting their recruitment and adhesion to the endothelium [14], and influence the responsiveness of platelets to various agonists [15]. Modified forms of Lp(a), some resembling oxidized Lp(a), have been identified in human atheromatous lesions [16]. In addition, ox-Lp(a) causes significant changes in apo(a) conformation, which could enhance the interaction of these particles with plasminogen binding sites as well as macrophage scavenger receptors, resulting in increased inhibitory effect on plasminogen activation and finally leading to attenuate fibrinolytic activity [17].Ox-Lp(a) has been reported to play more potent role than native Lp(a) in atherosclerosis [10,14,17,18], and autoantibodies against ox-Lp(a), Lp(a) immune complexes [Lp(a)-IC] have also been detected in vivo simultaneously [19,20]. The present review article focuses specifically on the relationship between Lp(a) oxidation, autoimmune and atherosclerosis together with our recent work. The pathogenic role of oxidized Lp(a)Lp(a) contains a large specific glycoprotein called apo(a), attached by a single disulfide bridge to apoB 100 of LDL (Figure 1). The adverse cardiovascular qualities of Lp(a) have been related to both its LDL-like properties (i.e., formation of foam cells) and its presumed role in fibrinolysis. www.intechopen.comCoronary Artery Disease -New Insights and Novel Approaches 50 Lp(a) oxidationThe structure, fatty acid composition, and antioxidant concentrations of Lp(a) and LDL are quite similar [21]. In vitro studies have shown that Lp(a) can be modified by oxidation (both chemical and cellular-mediated) in a fashion similar to LDL [22]. This modification, which involved lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS), caused marked changes in the structure and biological properties of Lp(a). Relative to native Lp(a), oxidized particles showed decreases of free amino groups and protein fragmentation, increased negative charge, and high aggregation ability. They were taken up and degraded readily by human monocyte/macrophages by means of scavenger receptors, a known pathway for clearance of ox-LDL in atheroma, inducing cholesteryl ester accumulation and promoting their transformation into foam cells within the arterial w...

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Section: The Clinical Value Of Circulating Oxidized Lp(a)supporting

confidence: 63%

Lipoprotein(a) Oxidation, Autoimmune and Atherosclerosis

Wang¹

2012

Coronary Artery Disease - New Insights and Novel Approaches

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“…15,16 Recognition of these oxidized phospholipids by a specific antibody, EO6 (an IgM autoantibody that recognizes the phosphatidylcholine head group in oxidized, but not in unoxidized, phospholipids containing arachidonic acid in the sn-2 position), has enabled them to be identified in atherosclerotic lesions in animals and humans. 28 The 12/15-lipoxygenase pathway, 15,16,29 -33 the 5-lipoxygenase pathway, 34 -36 the myeloperoxidase pathway, 37-43 the cycloxogenase pathways, 44 -46 and the NADPH oxidase pathways 47,48 have all been implicated in atherogenesis. The work of Blair et al 49,50 has shown that bifunctional electrophiles (␣, ␤-␤ unsaturated aldehyde genotoxins) such as 4-oxo-2-noneal can be formed from different lipid hydroperoxides by the action of trace metal ions or by vitamin C. The possibility that 4-oxo-2-noneal acts on LDL to produce biologically active oxidized phospholipids that are recognized by EO6 may explain how the genetic manipulation of multiple pathways producing different lipid hydroperoxides can influence atherogenesis.…”

Section: Role Of Oxidation In Atherogenesismentioning

confidence: 99%

Antiinflammatory Properties of HDL

Barter

Nicholls

Rye

et al. 2004

Circulation Research

1,189

786

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Abstract-There are several well-documented functions of high-density lipoprotein (HDL) that may explain the ability of these lipoproteins to protect against atherosclerosis. The best recognized of these is the ability of HDL to promote the efflux of cholesterol from cells. This process may minimize the accumulation of foam cells in the artery wall. However, HDL has additional properties that may also be antiatherogenic. For example, HDL is an effective antioxidants. The major proteins of HDL, apoA-I and apoA-II, as well as other proteins such as paraoxonase that cotransport with HDL in plasma, are well-known to have antioxidant properties. As a consequence, HDL has the capacity to inhibit the oxidative modification of low-density lipoprotein (LDL) in a process that reduces the atherogenicity of these lipoproteins. HDL also possesses other antiinflammatory properties. By virtue of their ability to inhibit the expression of adhesion molecules in endothelial cells, they reduce the recruitment of blood monocytes into the artery wall. These antioxidant and antiinflammatory properties of HDL may be as important as its cholesterol efflux function in terms of protecting against the development of atherosclerosis.

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“…OxPLs are highly prevalent in human vulnerable plaques ( 18 ) and in total chronic coronary occlusions ( 19 ). We have demonstrated that plasma OxPL/apoB levels identify angiographically-determined coronary artery disease (CAD) ( 14 ), predict the presence and progression of carotid and femoral atherosclerosis ( 20 ) and development of symptomatic peripheral arterial disease ( 21 ), and are elevated following acute coronary syndromes ( 12 ) and following percutaneous coronary intervention ( 22 ). Importantly, increased baseline levels of OxPL/apoB predict 15 year occurrence of new CVD events in previously healthy subjects independent of traditional risk factors and their Genetic architecture of PLG and apo(a).…”

mentioning

confidence: 99%