Endothelial progenitor cell dysfunction in rheumatic disease

Westerweel, Peter E.; Verhaar, Marianne C.

doi:10.1038/nrrheum.2009.81

Cited by 56 publications

(50 citation statements)

References 87 publications

(140 reference statements)

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“…33 However, the mechanisms underlying this pathogenetic correlation remain to be elucidated. Our results indicate that leukocyte ROS production, particularly by neutrophils, is significantly enhanced in BD patients.…”

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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Section: Discussionmentioning

confidence: 99%

Neutrophil Activation Promotes Fibrinogen Oxidation and Thrombus Formation in Behçet Disease

et al. 2016

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“…To eliminate this difficult transition, we have always used human cells throughout our initial research. However, multiple studies have clearly demonstrated that donor age and health status can dramatically affect cell behavior [Phillips et al, 1994;Becerra et al, 1996;Michel et al, 1996;Mogford et al, 2002;Heeschen et al, 2004;Zhang et al, 2005;Garolla et al, 2009;Krenning et al, 2009;Westerweel and Verhaar, 2009]. Thus, the second translational step was to use age-and risk-matched human cells.…”

Section: Preclinical Studies With the Lifeline Tm Graftmentioning

confidence: 99%

The Evolution of Vascular Tissue Engineering and Current State of the Art

Peck

Gebhart²,

Dusserre³

et al. 2011

Cells Tissues Organs

158

122

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Dacron® (polyethylene terephthalate) and Goretex® (expanded polytetrafluoroethylene) vascular grafts have been very successful in replacing obstructed blood vessels of large and medium diameters. However, as diameters decrease below 6 mm, these grafts are clearly outperformed by transposed autologous veins and, particularly, arteries. With approximately 8 million individuals with peripheral arterial disease, over 500,000 patients diagnosed with end-stage renal disease, and over 250,000 patients per year undergoing coronary bypass in the USA alone, there is a critical clinical need for a functional small-diameter conduit [Lloyd-Jones et al., Circulation 2010;121:e46–e215]. Over the last decade, we have witnessed a dramatic paradigm shift in cardiovascular tissue engineering that has driven the field away from biomaterial-focused approaches and towards more biology-driven strategies. In this article, we review the preclinical and clinical efforts in the quest for a tissue-engineered blood vessel that is free of permanent synthetic scaffolds but has the mechanical strength to become a successful arterial graft. Special emphasis is given to the tissue engineering by self-assembly (TESA) approach, which has been the only one to reach clinical trials for applications under arterial pressure.

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“…Microvascular endothelial cells challenged with inflammatory stimuli expressed the membrane-bound form of KitL and recruited EPCs via a c-Kit-mediated activation of the Akt signaling pathway to inflamed endothelium (18). However, chronic inflammatory processes or excessive inflammatory stimuli have deleterious effects, resulting in decreased EPCs in the circulation (4,119,126). Low levels of circulating CD133=KDRþ EPC also predicted occurrence of coronary atherosclerosis in rheumatoid arthritis (134).…”

Section: Inflammatory Diseasesmentioning

confidence: 99%

Critical Role of the Nitric Oxide/Reactive Oxygen Species Balance in Endothelial Progenitor Dysfunction

Fleißner

Thum²

2011

Antioxidants & Redox Signaling

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Endothelial injury and dysfunction are critical events in the pathogenesis of cardiovascular disease. During these processes, an impaired balance of nitric oxide bioavailability and oxidative stress is mechanistically involved. Circulating angiogenic cells (including early and late outgrowth endothelial progenitor cells (EPC)) contribute to formation of new blood vessels, neovascularization, and homeostasis of the vasculature, and are highly sensitive for misbalance between NO and oxidative stress. We here review the role of the endothelial nitric oxide synthase and oxidative stress producing enzyme systems in EPC during cardiovascular disease. We also focus on the underlying molecular mechanisms and potential emerging drug-and gene-based therapeutic strategies to improve EPC function in cardiovascular diseased patients. Antioxid. Redox Signal. 15, 933-948.

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Endothelial progenitor cell dysfunction in rheumatic disease

Cited by 56 publications

References 87 publications

Neutrophil Activation Promotes Fibrinogen Oxidation and Thrombus Formation in Behçet Disease

Neutrophil Activation Promotes Fibrinogen Oxidation and Thrombus Formation in Behçet Disease

The Evolution of Vascular Tissue Engineering and Current State of the Art

Critical Role of the Nitric Oxide/Reactive Oxygen Species Balance in Endothelial Progenitor Dysfunction

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