The Many Antithrombotic Actions of Nitric Oxide

Tziros, Constantine; Freedman, Jane E.

doi:10.2174/138945006778559111

Cited by 37 publications

(30 citation statements)

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“…Because VEGF mediates fibrinolytic processes, drug-mediated VEGF suppression may inactivate enzymes in the plasminogen activator pathway and decrease the synthesis of matrix metalloproteinases, 72,73 thereby leading to the oversynthesis of matrix proteins. Other possible mechanisms include the down-regulation of nitric oxide (a natural antithrombotic agent), 74 increased endothelial cell apoptosis, 75 increased erythropoietin synthesis (which increases blood viscosity), 76 and destabilization of cholesterol plaques. 77 Adverse events that have been attributed to VEGF suppression are represented in Figure 4.…”

Section: Systemic Concernsmentioning

confidence: 99%

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

Stewart

2012

Mayo Clinic Proceedings

166

105

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Vascular endothelial growth factor (VEGF) plays an important role in both physiologic and pathologic angiogenesis and contributes to increased permeability across both the blood-retinal and blood-brain barriers. After 2 decades of extensive research into the VEGF families and receptors, specific molecules have been targeted for drug development, and several medications have received US Food and Drug Administration approval. Bevacizumab, a full-length antibody against VEGF approved for the intravenous treatment of advanced carcinomas, has been used extensively in ophthalmology for exudative age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, retinopathy of prematurity, and other chorioretinal vascular disorders. Pegaptanib and ranibizumab have been developed specifically for intraocular use, whereas the soon-to-be-introduced aflibercept (VEGF Trap-Eye) is moving through clinical trials for both intraocular and systemic use. Although these drugs exhibit excellent safety profiles, ocular and systemic complications, particularly thromboembolic events, remain a concern in patients receiving therapy. Patients experiencing adverse events that may be related to VEGF suppression should be carefully evaluated by both the ophthalmologist and the medical physician to reassess the need for intraocular therapy and explore the feasibility of changing medications. For this review a search of PubMed from January 1, 1985 through April 15, 2011, was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, diabetic retinopathy, retina vein occlusions, retinopathy of prematurity, intravitreal injections, bevacizumab, ranibizumab, and VEGF Trap. Studies were limited to those published in English. Other articles were identified from bibliographies of retrieved articles and archives of the author.

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Section: Systemic Concernsmentioning

confidence: 99%

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

Stewart

2012

Mayo Clinic Proceedings

166

105

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“…Decreased NO released from platelets is proposed to diminish negative feedback loops and potentially further promote platelet activation and aggregation, contributing to a pro-thrombotic condition. As NO bioavailability in the vascular system has been associated with various disease states, genetic variants or medications that enhance NO bioavailability may be used as a means to improve endothelial function and reduce cardiovascular complications [23]. As NO has the role of interfering with the process of thrombus formation, it is a possible target for the antithrombotic modulation by pENW.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of nitric oxide production contributes to the antiplatelet and antithrombotic effect of new peptide pENW (pGlu-Asn-Trp)

Liu¹,

Luo²,

Yang³

et al. 2015

Thrombosis Research

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“…Nitric oxide (NO) is intimately involved in maintaining vascular integrity and blood flow; it is also a potent inhibitor of platelet aggregation ( Fig. 1; for recent review see [1]). NO generated by endothelial NO synthase (NOS) plays an important role in averting inappropriate thrombus formation at a vessel wall.…”

Section: Introductionmentioning

confidence: 99%

Platelet Hyperaggregability: Impaired Responsiveness to Nitric Oxide (“Platelet NO Resistance”) as a Therapeutic Target

Rajendran

Chirkov

2008

Cardiovasc Drugs Ther

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Platelet hyperaggregability and associated thrombosis have been documented in a number of cardiovascular disease states. While one of the current mainstays of anti-thrombotic treatment (i.e. aspirin, clopidogrel, glycoprotein IIb/IIIa antagonists) has been directed at reducing platelet activation and aggregation, it is apparent that there are limitations to the effectiveness of these therapies. Nitric oxide (NO) plays an important role in platelet physiology. The ability of NO to regulate cyclic guanosine-3,'5'-monophosphate (cGMP), via activation of soluble guanylate cyclase, is the principal mechanism of negative control over platelet activity. NO is not only of the endothelial source, it is also released from activated platelets, providing a negative feedback. Studies in patients with symptomatic ischemia, chronic heart failure, diabetes and various risk factors for cardiovascular disease have demonstrated that platelets from these subjects exhibit reduced responsiveness to the anti-aggregating efficacy of NO: a phenomenon termed "platelet NO resistance". It constitutes an impaired physiological response to endogenous NO (endothelium-derived relaxing factor or EDRF), and as such may contribute to the increased risk of ischemic events. NO resistance also accounts for reduced pharmaco-activity of exogenous NO donors, e.g. organic nitrates. Platelet NO resistance results largely from a combination of "scavenging" of NO by superoxide anion radical and inactivation of soluble guanylate cyclase. NO resistance has both diagnostic and prognostic implications. The current review examines the association of platelet NO resistance with pathological hyperaggregability and discusses potential therapeutic strategies targeting this abnormality.

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The Many Antithrombotic Actions of Nitric Oxide

Cited by 37 publications

References 0 publications

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

Stimulation of nitric oxide production contributes to the antiplatelet and antithrombotic effect of new peptide pENW (pGlu-Asn-Trp)

Platelet Hyperaggregability: Impaired Responsiveness to Nitric Oxide (“Platelet NO Resistance”) as a Therapeutic Target

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