Fibrinogen is an efficient antioxidant

Olinescu, R; Kummerow, Fred A.

doi:10.1016/s0955-2863(00)00147-9

Cited by 42 publications

(27 citation statements)

References 43 publications

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“…In the present study, both plasma PC and fibrinogen PC were markedly and significantly increased in patients with post-AMI when compared with control subjects and were significantly correlated. In this context, previous reports indicate that fibrinogen is more susceptible to oxidation than most other plasma proteins; 12 in particular, fibrinogen is 20× more susceptible to oxidation than albumin, 13 as also reported in patients with MI, where it was found that total plasma carbonyls were formed preferentially on fibrinogen. When we investigated, using far-UV circular dichroism spectroscopy, whether the alterations observed in fibrinogen functions could be related to secondary structure modifications, we found a shift in the mean residual ellipticity and a reduction in α-helical content in patients with post-AMI in comparison with controls, suggesting a change in secondary structure content.…”

Section: 8mentioning

confidence: 54%

Oxidative Modification of Fibrinogen Is Associated With Altered Function and Structure in the Subacute Phase of Myocardial Infarction

Becatti

Marcucci

et al. 2014

ATVB

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Objective-Among plasma proteins, fibrinogen represents a major target of oxidative modifications. In patients with postacute myocardial infarction (6 months after the acute event), fibrinogen oxidation-induced carbonyls and fibrinogen function were estimated using in vitro and ex vivo approaches. Fibrinogen structural features and clot architecture were also explored. Approach and Results-In 39 patients with post-acute myocardial infarction and 28 age-, sex-, and risk factor-matched controls, oxidative stress markers (in plasma and in purified fibrinogen fractions), thrombin-catalyzed fibrin polymerization, and plasmin-induced fibrin lysis were estimated. Circular dichroism spectra of purified fibrinogen extracts, electron microscopy, and differential interference contrast microscopy analyses of fibrin clots were also performed. Marked signs of oxidative stress in plasma (P<0.01 versus controls) and, correspondingly, an increased extent of fibrinogen carbonylation (3.5-fold over control values; P<0.01 versus controls) were observed in patients. Furthermore, fibrinogen fractions purified from patients exhibited significantly reduced clotting ability and decreased susceptibility to plasmininduced lysis (P<0.01 versus controls). Alterations in fibrinogen secondary structure, as suggested by circular dichroism spectroscopy, and in fibrin clot architecture, as analyzed by electron and differential interference contrast microscopy, were also identified. Conclusions-Here, we report for the first time that patients with post-acute myocardial infarction present with an overall imbalance in redox status and marked fibrinogen carbonylation associated with altered fibrinogen function, thus suggesting a role for carbonylation as a direct mechanism of fibrinogen function. The observed features occur along with modifications in protein structure and in clot architecture. Results SubjectsDemographic and clinical characteristics of the population studied are summarized in Table 1. Oxidative Stress Markers in Plasma and in FibrinogenAs reported in Table 2, patient plasma displayed significantly higher total PC and thiobarbituric acid reactive substances levels, and lower total antioxidant capacity, than healthy controls (P<0.05 versus controls). Plasma total PC was positively and significantly correlated with fibrinogen PC (P<0.05; R=0.555; Figure 1A) and with thiobarbituric acid reactive substances levels (P<0.05; R=0.444; Figure 1B). Purified fibrinogen from patients displayed significantly increased carbonylation (3.5-fold) in comparison with healthy controls (P<0.01; Figure 1C). PC amounts obtained in human, 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-challenged purified fibrinogen (SIGMA, Milan, Italy) were comparable with those observed in fibrinogen from patients with post-AMI and resulted significantly increased compared with untreated fibrinogen (Table 3). Circular Dichroism Spectra: Analysis of Secondary StructureSecondary protein structure was analyzed by far-UV circular dichroism spectroscopy (Figure 2). In ...

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Section: 8mentioning

confidence: 54%

Oxidative Modification of Fibrinogen Is Associated With Altered Function and Structure in the Subacute Phase of Myocardial Infarction

Becatti

Marcucci

et al. 2014

ATVB

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“…In this context, it has been reported that fibrinogen is more prone to oxidation than albumin, and on oxidation, clot formation rate has been observed to be decreased. 39,40 However, other investigators reported that exposure of fibrinogen to oxidizing conditions (ie, Fe 3+ ascorbate) promoted fibrin formation, enhanced platelet aggregation, and supported less efficient plasminogen activation by tissue plasminogen activator. 41 Figure 7.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Activation Promotes Fibrinogen Oxidation and Thrombus Formation in Behçet Disease

et al. 2016

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Background-Behçet disease (BD) is a systemic vasculitis with a broad range of organ involvement, characterized by a multisystemic, immune-inflammatory disorder involving vessels of all sizes and often complicated by thrombosis. Systemic redox imbalance and circulating neutrophil hyperactivation have been observed in BD patients and are thought to be responsible for impaired coagulation. We here focused on the pathogenetic mechanisms potentially linking immune cell activation and thrombosis, and specifically examined whether neutrophil activation can affect fibrinogen modifications and consequently elicit thrombosis. Methods and Results-Blood samples were collected from 98 consecutive BD patients attending our dedicated Center and from 70 age-and sex-matched healthy controls; in all patients fibrinogen function and structure, fibrin susceptibility to plasmin-lysis, plasma redox status, leukocyte oxidative stress markers, and possible reactive oxygen species sources were examined. Thrombin-catalyzed fibrin formation and fibrin susceptibility to plasmin-induced lysis were significantly impaired in BD patients (P<0.001). These findings were associated with increased plasma oxidative stress markers (P<0.001) and with a marked carbonylation of fibrinogen (P<0.001), whose secondary structure appeared deeply modified. Neutrophils displayed an enhanced NADPH oxidase activity and increased reactive oxygen species production (P<0.001), which significantly correlated with fibrinogen carbonylation level (r 2 =0.33, P<0.0001), residual β-band intensity (r 2 =0.07, P<0.01), and fibrinogen clotting ability (r 2 =0.073, P<0.01) Conclusions-In BD patients, altered fibrinogen structure and impaired fibrinogen function are associated with neutrophil activation and enhanced reactive oxygen species production whose primary source is represented by neutrophil NADPH oxidase. Becatti et al Role of Neutrophils in Thrombus Formation 303for the management of BD suggest that thrombosis should be treated with immunosuppression rather than anticoagulation, 17 as an inflammation-induced thrombosis. Recent studies have provided evidence that fibrinogen plays a multifaceted role in inflammatory responses and autoimmunity. 18,19 The ability of fibrinogen to participate in the inflammatory response depends on its specific interaction with integrins, the leukocyte cell surface adhesion receptors. M2 (CD11b/CD18, Mac-1) and X2 (CD11c/CD18, p150,95) are the main fibrinogen receptors and are expressed on neutrophils, monocytes, macrophages and several subsets of lymphocytes. 20 In BD, endothelial cell dysfunction, increased reactive oxygen species (ROS) production, 21 and neutrophil hyperfunction have been reported, 15 together with an impaired fibrinolysis. 22 In this study, to highlight the mechanisms of inflammation-induced thrombosis, we investigated fibrinogen modifications, fibrin susceptibility to plasmin-lysis, plasma redox status, leukocyte oxidative stress, and possible ROS sources in a population of BD patients. Moreover, we explored fib...

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“…Fibrinogen oxidation following exposure to oxygen, metal, and myeloperoxidase-derived oxidants decreases the rate of clot formation. 65 However, other investigators reported that exposure of fibrinogen to Fe 3ϩ ascorbate promotes fibrin formation, enhances platelet aggregation, and supports less efficient plasminogen activation by tPA. 66,67 Studies on air pollution have shown that ultrafine particulate matter can modulate fibrin structure in an oxidation-dependent manner.…”

Section: Oxidative Stressmentioning

confidence: 99%

“…65 Fibrinogen may therefore scavenge oxidants and protect other proteins from oxidation. Fibrinogen oxidation following exposure to oxygen, metal, and myeloperoxidase-derived oxidants decreases the rate of clot formation.…”

Section: Oxidative Stressmentioning

confidence: 99%

Fibrin Clot Structure and Function

Undas

Ariëns

2011

ATVB

439

200

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Abstract-The formation of fibrin clots that are relatively resistant to lysis represents the final step in blood coagulation. We discuss the genetic and environmental regulators of fibrin structure in relation to thrombotic disease. In addition, we discuss the implications of fibrin structure for treatment of thrombosis. Fibrin clots composed of compact, highly branched networks with thin fibers are resistant to lysis. Altered fibrin structure has consistently been reported in patients with several diseases complicated by thromboembolic events, including patients with acute or prior myocardial infarction, ischemic stroke, and venous thromboembolism. Relatives of patients with myocardial infarction or venous thromboembolism display similar fibrin abnormalities. Low-dose aspirin, statins, lowering of homocysteine, better diabetes control, smoking cessation, and suppression of inflammatory response increase clot permeability and susceptibility to lysis. Growing evidence indicates that abnormal fibrin properties represent a novel risk factor for arterial and venous thrombotic events, particularly of unknown etiology in young and middle-aged patients. (Arterioscler Thromb Vasc Biol. 2011;31:e88-e99.)

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Fibrinogen is an efficient antioxidant

Cited by 42 publications

References 43 publications

Oxidative Modification of Fibrinogen Is Associated With Altered Function and Structure in the Subacute Phase of Myocardial Infarction

Oxidative Modification of Fibrinogen Is Associated With Altered Function and Structure in the Subacute Phase of Myocardial Infarction

Neutrophil Activation Promotes Fibrinogen Oxidation and Thrombus Formation in Behçet Disease

Fibrin Clot Structure and Function

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