The Effect of Dipyridamole on Vascular Cell-Derived Reactive Oxygen Species

Chakrabarti, Subrata; Vitseva, Olga; Iyú, David; Varghese, Sonia; Freedman, Jane E.

doi:10.1124/jpet.105.089987

Cited by 48 publications

(36 citation statements)

References 37 publications

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“…The number of HUVECs in each well was evaluated using 10% Alamar Blue, added 2 h before the adhesion assay. Alamar Blue does not interfere with the treatment but still allows the evaluation of cell numbers following excitation at 550 nm and emission at 570 nm, as described [20].…”

Section: Adhesion Of Monocytic Thp1 Cells To the Endothelial Layermentioning

confidence: 99%

Hypoxia influences CD40–CD40L mediated inflammation in endothelial and monocytic cells

et al. 2009

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Section: Adhesion Of Monocytic Thp1 Cells To the Endothelial Layermentioning

confidence: 99%

Hypoxia influences CD40–CD40L mediated inflammation in endothelial and monocytic cells

et al. 2009

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“…61 At therapeutically relevant concentrations, dipyridamole suppresses the formation of reactive oxygen species in platelets and endothelial cells and improves cellular redox status, with data suggesting that the redox-dependent properties of dipyridamole have a direct effect on vascular cells. 62 In addition, dipyridamole enhances platelet inhibition by amplifying the signaling of NO donors suggesting that enhancement of endothelium-dependent NO/cGMP-mediated signaling may be a relevant component of dipyridamole effect. 63 Polymeric flavonoids, such as those found in red wine and purple grapes, contain antioxidant properties believed to be protective against cardiovascular events.…”

Section: The Effect Of Therapeutics On Platelet-dependent Oxidative Smentioning

confidence: 99%

Oxidative Stress and Platelets

Freedman

2008

ATVB

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283

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Abstract-Platelet-dependent thrombus formation may be influenced by alteration of platelet or vascular redox state, the presence of endogenous or exogenous antioxidants, as well as the formation of reactive oxygen and nitrogen species. Specifically, settings and pathways that influence the formation of superoxide and nitric oxide, as well as their metabolism, may influence platelet function and thrombus formation. Although some antioxidant regimens have been associated with bleeding and hemorrhagic stroke, the therapeutic value of antioxidants in clinical syndromes that lead to platelet-dependent thrombosis is not clear, as supplemental antioxidants have not been generally associated with better cardiovascular outcome. R edox changes occur as a function of normal platelet activation; however, the introduction of additional oxidative stress in certain settings may be prothrombotic. Modulation of platelet or vascular redox status, the presence of reactive oxygen species, and the addition of exogenous antioxidants can alter platelet activation in vitro and in vivo and may have (patho)physiological ramifications.The clinical role of oxidative stress in platelet function and thrombosis is not straightforward. Although earlier epidemiological studies found that dietary antioxidant consumption was inversely associated with the development of coronary artery disease, more recent studies of vitamin supplementation have presented conflicting or negative results. 1 Interestingly, some of the negative side effects of antioxidant therapies, such as enhanced hemorrhagic stroke, may be attributed to changes in the thrombotic response. Although the effects of antioxidants were attributed to the prevention of oxidative modification of low-density lipoprotein (LDL) and the inhibition of atherogenesis, other effects may be relevant, including regulation of platelet activation, which is dependent on the balance between oxidative stress and redox state. As platelet function has also been implicated in the development of atherosclerosis and in the acute occlusion of coronary vessels, 2,3 oxidative processes and platelet redox status may have far reaching effects on the homeostasis of vasculature. Platelet Activation, Cardiovascular Events, and the Role of AntioxidantsThrombus formation within a coronary vessel is the precipitating event in myocardial infarction and unstable angina. 4 Normally, the intact endothelium prevents adhesion and activation of platelets. Adhesion of platelets to the endothelium is prevented by several mechanisms, including endothelial cell production of prostacyclin and nitric oxide (NO). 5,6 The occurrence of superficial intimal injury caused by endothelial denudation and deep intimal injury caused by plaque rupture expose collagen and von Willebrand factor (vWF) to platelets. Platelets then adhere directly to collagen or indirectly via the binding of vWF to the glycoprotein (GP) Ib/IX matrix. Local platelet activation stimulates further thrombus formation and additional platelet recruitment by supporting ce...

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“…24 Furthermore, DP suppresses oxygen free radical formation in platelets and endothelial cells and improves cellular redox status. 25 These antixodiative effects of DP may extend the half-life and increase the bioavailability of endothelium-derived nitric oxide (NO), which is vascular protective.…”

Section: Antioxidative Effectsmentioning

confidence: 99%

Translational Therapeutics of Dipyridamole

Kim

Liao

2008

ATVB

120

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Abstract-Dipyridamole (DP) is a phosphodiesterase inhibitor that increases the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanine monophosphate (cGMP) by preventing their conversion to AMP and GMP, respectively. By increasing cAMP and cGMP levels in platelets, DP reversibly inhibits platelet aggregation and platelet-mediated thrombotic disease. In addition, DP may potentiate some of the vascular protective effects of endothelium-derived nitric oxide (NO), which increases cGMP by stimulating soluble guanylyl cyclase. Endotheliumderived NO is an important regulator of vascular tone, blood flow, and tissue perfusion. Indeed, endothelial NO synthase-deficient (eNOS Ϫ/Ϫ ) mice exhibit elevated systemic blood pressure and have larger myocardial and cerebral infarct size after ischemic injury. Other NO/cGMP-dependent effects that may be potentiated by DP include inhibition of vascular smooth muscle proliferation and prevention of endothelial-leukocyte interaction. In addition, DP increases local concentrations of adenosine and prostacyclin, which could affect vascular tone and inflammation. Finally, DP has antioxidant properties, which could stabilize platelet and vascular membranes as well as prevent the oxidation of low-density lipoprotein. These platelet and nonplatelet actions of DP may contribute to some of its therapeutic benefits in vascular disease. (Arterioscler Thromb Vasc Biol. 2008;28:s39-s42)

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The Effect of Dipyridamole on Vascular Cell-Derived Reactive Oxygen Species

Cited by 48 publications

References 37 publications

Hypoxia influences CD40–CD40L mediated inflammation in endothelial and monocytic cells

Hypoxia influences CD40–CD40L mediated inflammation in endothelial and monocytic cells

Oxidative Stress and Platelets

Translational Therapeutics of Dipyridamole

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