<i>In vitro</i> evaluation of the safe margin, antithrombotic and antiproliferative actions for the treatment of restenosis: Nitric oxide donor and polymers

Sorragi, Cláudia de Lourdes; Shishido, Sı́lvia Mika; Lemos, Maria Edwiges; Marcondes, Sissi; Antunes, Edson; Krieger, Marta Helena

doi:10.1002/cbf.1738

Cited by 15 publications

(11 citation statements)

References 48 publications

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“…Accordingly, fibrin agglomerates seemingly play a beneficial role in clearing fibrin fragments during fibrinolysis, or a potentially deleterious role if generated under coagulation conditions and not removed from the circulation. This may be of significance in the design of drug-eluting stents to prevent restenosis, where GSNO is combined with a polymeric coating, and has the property of inhibiting platelet aggregation with an EC50 of 5.0 mM [28]. Our results suggest this concentration of GSNO could induce local formation of fibrin agglomerates that may enter the circulation and potentially plug the downstream microcirculation.…”

Section: Discussionmentioning

confidence: 72%

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S-Nitrosoglutathione Acts as a Small Molecule Modulator of Human Fibrin Clot Architecture

et al. 2012

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BackgroundAltered fibrin clot architecture is increasingly associated with cardiovascular diseases; yet, little is known about how fibrin networks are affected by small molecules that alter fibrinogen structure. Based on previous evidence that S-nitrosoglutathione (GSNO) alters fibrinogen secondary structure and fibrin polymerization kinetics, we hypothesized that GSNO would alter fibrin microstructure.Methodology/Principal FindingsAccordingly, we treated human platelet-poor plasma with GSNO (0.01–3.75 mM) and imaged thrombin induced fibrin networks using multiphoton microscopy. Using custom designed computer software, we analyzed fibrin microstructure for changes in structural features including fiber density, diameter, branch point density, crossing fibers and void area. We report for the first time that GSNO dose-dependently decreased fibrin density until complete network inhibition was achieved. At low dose GSNO, fiber diameter increased 25%, maintaining clot void volume at approximately 70%. However, at high dose GSNO, abnormal irregularly shaped fibrin clusters with high fluorescence intensity cores were detected and clot void volume increased dramatically. Notwithstanding fibrin clusters, the clot remained stable, as fiber branching was insensitive to GSNO and there was no evidence of fiber motion within the network. Moreover, at the highest GSNO dose tested, we observed for the first time, that GSNO induced formation of fibrin agglomerates.Conclusions/SignificanceTaken together, low dose GSNO modulated fibrin microstructure generating coarse fibrin networks with thicker fibers; however, higher doses of GSNO induced abnormal fibrin structures and fibrin agglomerates. Since GSNO maintained clot void volume, while altering fiber diameter it suggests that GSNO may modulate the remodeling or inhibition of fibrin networks over an optimal concentration range.

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Section: Discussionmentioning

confidence: 72%

“…Additionally, GSNO modulates hemostasis by inhibiting platelet activation and aggregation, and decreasing fibrinogen binding to platelets [22]–[25]. GSNO has been used clinically as an antithrombotic agent [26], [27] and is also being incorporated into drug-eluting stents to prevent restenosis [28].…”

Section: Introductionmentioning

confidence: 99%

S-Nitrosoglutathione Acts as a Small Molecule Modulator of Human Fibrin Clot Architecture

et al. 2012

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“…More recently, Sorragi et al carried out cytotoxicity studies using GSNO donors combined with poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) in aqueous solution (PVA/PVP/GSNO) for coating DES 64. Cell growth studies found that both GSNO and PVA/PVP/GSNO induced anti‐proliferative effects in rabbit SMCs and inhibited platelet aggregation.…”

Section: No‐generating Materialsmentioning

confidence: 99%

Nitric Oxide Donors for Cardiovascular Implant Applications

Naghavi

Mel

Alavijeh

et al. 2012

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123

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In an era of increased cardiovascular disease burden in the ageing population, there is great demand for devices that come in to contact with the blood such as heart valves, stents, and bypass grafts that offer life saving treatments. Nitric oxide (NO) elution from healthy endothelial tissue that lines the vessels maintains haemostasis throughout the vasculature. Surgical devices that release NO are desirable treatment options and N-diazeniumdiolates and S-nitrosothiols are recognized as preferred donor molecules. There is a keen interest to investigate newer methods by which NO donors can be retained within biomaterials so that their release and kinetic profiles can be optimized. A range of polymeric scaffolds incorporating microparticles and nanomaterials are presenting solutions to current challenges, and have been investigated in a range of clinical applications. This review outlines the application of NO donors for cardiovascular therapy using biomaterials that release NO locally to prevent thrombosis and intimal hyperplasia (IH) and enhance endothelialization in the fabrication of next generation cardiovascular device technology.

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“…For example, poly(vinyl alcohol) and poly(vinyl pyrrolidone) polymer solutions reduced the cytotoxicity and enhanced the anti-proliferative effects of GSNO in smooth muscle cell cultures. [56] In this section, recent research on the development of polymer-based NO-releasing and -generating materials without evaluation in vivo are discussed (2006–2011) (Scheme 1). Previous research work on this topic has been reviewed elsewhere.…”

Section: Novel No-releasing and No-generating Polymeric Materialsmentioning

confidence: 99%

Polymer‐Based Nitric Oxide Therapies: Recent Insights for Biomedical Applications

Jen¹,

Serrano²,

Lith³

et al. 2011

Adv Funct Materials

163

152

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Since the discovery of nitric oxide (NO) in the 1980s, this cellular messenger has been shown to participate in diverse biological processes such as cardiovascular homeostasis, immune response, wound healing, bone metabolism, and neurotransmission. Its beneficial effects have prompted increased research in the past two decades, with a focus on the development of materials that can locally release NO. However, significant limitations arise when applying these materials to biomedical applications. This Feature Article focuses on the development of NO-releasing and NO-generating polymeric materials (2006–2011) with emphasis on recent in vivo applications. Results are compared and discussed in terms of NO dose, release kinetics, and biological effects, in order to provide a foundation to design and evaluate new NO therapies.

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In vitro evaluation of the safe margin, antithrombotic and antiproliferative actions for the treatment of restenosis: Nitric oxide donor and polymers

Cited by 15 publications

References 48 publications

S-Nitrosoglutathione Acts as a Small Molecule Modulator of Human Fibrin Clot Architecture

S-Nitrosoglutathione Acts as a Small Molecule Modulator of Human Fibrin Clot Architecture

Nitric Oxide Donors for Cardiovascular Implant Applications

Polymer‐Based Nitric Oxide Therapies: Recent Insights for Biomedical Applications

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