The role of β2-glycoprotein I (β2GPI) in the activation of plasminogen

López-Lira, Francisco; Rosales-León, Luis; Martinez, V.; Ordaz, Blanca H. Ruiz

doi:10.1016/j.bbapap.2005.12.020

Cited by 40 publications

(32 citation statements)

References 28 publications

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“…β 2 GPI is the main target antigen for antiphospholipid antibodies in patients with antiphospholipid syndrome, and has been shown to regulate the activation of plasminogen. Although the exact physiological role of β 2 GPI is not well understood (Lopez-Lira et al, 2006), it is known that β 2 GPI forms complexes with oxidized LDL, which represent a common metabolic product relevant to atherogenesis and a risk factor or an indirect but significant contributor for atherothrombotic complications in autoimmune patients (Matsuura et al, 2006). Levels of another apolipoprotein, Apo A-I were also altered by dietary CoQ 10 , although in this case the protein was increased in the CoQ 10 -group (twofold at 24 months).…”

Section: Discussionmentioning

confidence: 99%

Modifications of plasma proteome in long-lived rats fed on a coenzyme Q10-supplemented diet

Santos‐González

Díaz

Navas

et al. 2007

Experimental Gerontology

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Dietary coenzyme Q 10 prolongs lifespan of rats fed on a PUFAn-6-enriched diet.Our aim was to analyze changes in the levels of plasma proteins of rats fed on a PUFAn-6 plus coenzyme Q 10 -based diet. This approach could give novel insights into the mechanisms of lifespan extension by dietary coenzyme Q 10 in the rat. Serum albumin, which decreases with aging in the rat, was significantly increased by coenzyme Q 10 supplementation both at 6 and 24 months. After depletion of the most abundant proteins by affinity chromatography, levels of less abundant plasma proteins were also studied by using 2D-electrophoresis and MALDI-TOF mass fingerprinting analysis. Our results have shown that lifelong dietary supplementation with coenzyme Q 10 induced significant decreases of plasma hemopexin, apolipoprotein H and interalpha-inhibitor H4P heavy chain (at both 6 and 24 months), preprohaptoglobin, fibrinogen γ-chain precursor, and fetuin-like protein (at 6 months), and alpha-1-antitrypsin precursor and type II peroxiredoxin (at 24 months). On the other hand, coenzyme Q 10 -supplementation resulted in significant increases of serine protease inhibitor 3, vitamin D-binding protein (at 6 months), and Apo A-I (at 24 months). Our results support a beneficial role of dietary coenzyme Q 10 decreasing oxidative stress and cardiovascular risk, and modulating inflammation during aging.

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Section: Discussionmentioning

confidence: 99%

Modifications of plasma proteome in long-lived rats fed on a coenzyme Q10-supplemented diet

Santos‐González

Díaz

Navas

et al. 2007

Experimental Gerontology

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“…Recently, studies showed that β 2 -GPI specifically interacted with LDL as well as ox-LDL, and formed complexes in the intima of atherosclerotic lesions, and then, these complexes were taken up by macrophages via anti-β 2 -GPI autoantibody-mediated phagocytosis, contributing to the development of atherosclerosis [70]. In vitro studies also demonstrated that β 2 -GPI bound Lp(a) with high affinity [71,72], suggesting that β 2 -GPI might bind Lp(a) to form complexes of β 2 -GPI with Lp(a) [β 2 -GPI-Lp(a)] in vivo. Furthermore, preliminary data suggest that additional ox-PL are present in the lipid phase of Lp(a) ( Figure 5) [73].…”

Section: Lp(a) Immune Complexes and β 2 -Glycoprotein I Complexes Witmentioning

confidence: 99%

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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“…The main plasminogen activators are tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) (4,5). Plasminogen is also activated by coagulation factor XII, thrombin, as well as some bacterial enzymes (6). In order to provide stable homeostatic conditions in the human body, contrary to the above mentioned activators, but constantly balancing with them, there are numerous inhibitors of the fibrinolytic mechanism, acting as inhibitors of both plasminogen and its activators.…”

Section: Introductionmentioning

confidence: 99%

Decrease of Fibrinolytic Potential in the Occurence of Cerebral Ischemia

Vučković¹,

Đerić²,

Ilić³

et al. 2008

Journal of Medical Biochemistry

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Summary:One of the most present clinical manifestations of long and progressive atherothrombotic occurrences is the ischemic cerebrovascular insult, one of the leading causes of death and illness in the world. Lately, a growing number of scientists believe that disorders in the fibrinolytic mechanism function are the key to the occurrence of cerebral ischemia. The goal of this study is to investigate whether the disorder of the fibrinolytic mechanism has influence on the occurrence of ischemic cerebrovascular insult. Our study includes 90 examinees, 60 of which suffer from ischemic cerebrovascular insult and 30 are clinically healthy examinees forming the control group. The results of our investigation show that statistically a significantly larger number of patients has decreased fibrinolytic potential comparing with controls (p<0.01). According to this, it has been noted that euglobulin lysis clot time in the patient group is significantly longer (p=0.005). Statistically, no significant difference has been noted related to the activity of plasminogen (p=0.085). Further on, the plasminogen activator inhibitor-1 values among the patients have been significantly higher (p=6.20×10 ). The results of this investigation impose the conclusions that the decrease in fibrinolytic potential affects the occurrence of ischemic cerebrovascular insult, that it is directly connected to the higher levels of plasminogen activator inhibitor-1 and that the growth of tissue-type plasminogen activator antigen concentration participates in the decrease of fibrinolytic potential among patients suffering from cerebral ischemia. Keywords: fibrinolytic system, plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor-1 Kratak sadr`aj: Jedna od naj~e{}ih klini~kih manifestacija dugotrajnih i progresivnih aterotrombotskih zbivanja je ishemijski cerebrovaskularni insult. To oboljenje se danas nalazi me|u vode}im uzrocima morbiditeta i mortaliteta u ve}ini zemalja. U poslednje vreme sve je ve}i broj nau~nika koji smatraju da su poreme}aji fibrinoliznog mehanizma kljuñ astanka cerebralne ishemije. Cilj na{e studije bio je upravo da ispitamo da li poreme}aj fibrinoliznog mehanizma ima uticaja na nastanak ishemijskog cerebrovaskularnog insulta. U studiju je uklju~eno 90 ispitanika, od toga 60 bolesnika koji su do`iveli cerebrovaskularni insult po tipu ishemije i 30 klini~ki zdravih osoba, koje su ~inile kontrolnu grupu. Rezultati na{eg istra`ivanja ukazuju na statisti~ki zna~ajno ve}i broj ispitanika sa suprimiranim fibrinoliznim potencijalom u grupi bolesnika u odnosu na kontrolnu grupu (p<0,01). U skladu s tim, ustanovljeno je statisti~ki zna~ajno du`e euglobulinsko vreme lize koaguluma me|u bolesnicima nego me|u kontrolama (p=0,005). Nije uo~ena statisti~ki zna~ajna razlika u aktivnosti plazminogena izme|u te dve grupe ispitanika (p=0,085), dok su vrednosti inhibitora aktivatora plazminogena-1 (p=6,20×10 -11 ) i antigena tkivnog aktivatora plazminogena (p=5,20×10 -5 ) statisti~ki zna~ajno vi{e u grupi bolesnika. Ov...

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The role of β2-glycoprotein I (β2GPI) in the activation of plasminogen

Cited by 40 publications

References 28 publications

Modifications of plasma proteome in long-lived rats fed on a coenzyme Q10-supplemented diet

Modifications of plasma proteome in long-lived rats fed on a coenzyme Q10-supplemented diet

Lipoprotein(a) Oxidation, Autoimmune and Atherosclerosis

Decrease of Fibrinolytic Potential in the Occurence of Cerebral Ischemia

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