Inhibitory effect of clopidogrel on platelet adhesion and intimal proliferation after arterial injury in rabbits.

Herbert, Jean‐Marc; Tissinier, A; Defreyn, G.; Maffrand, Jean‐Pierre

doi:10.1161/01.atv.13.8.1171

Cited by 109 publications

(61 citation statements)

References 32 publications

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“…52 These findings may explain the anti-restenotic effect of clopidogrel seen in an earlier animal model. 63 Recent data obtained with the active metabolite of clopidogrel and human platelets in vitro has reproduced the inhibitory effects of clopidogrel on platelet P-selectin expression and platelet/ polymorphonuclear neutrophil adhesion. Furthermore, these data have demonstrated an inhibitory effect of the clopidogrel active metabolite on platelet-dependent production of reactive oxygen species in neutrophils and on monocyte expression of tissue factor activity.…”

Section: Studies In Healthy Volunteersmentioning

confidence: 91%

Clinical evidence for anti-inflammatory effects of antiplatelet therapy in patients with atherothrombotic disease

et al. 2007

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Recent advances in our understanding of cardiovascular disease have revealed that atherothrombotic events, such as myocardial infarction and ischemic stroke, are the end result of a complex inflammatory response to multifaceted vascular pathology. As well as initiating thrombus formation at the site of a ruptured atherosclerotic plaque, platelets play a key role in vascular inflammation, through release of their own pro-inflammatory mediators and interactions with other relevant cell types (endothelial cells, leukocytes, and smooth muscle cells). An increasing body of literature shows that inflammatory biomarkers can be used to predict atherothrombotic risk and that antiplatelet therapy may reduce the levels of these markers. Acetylsalicylic acid (ASA) has been attributed with reducing levels of the transcription factor nuclear factor κB (NF-κB), C-reactive protein, and soluble CD40 ligand, although the evidence relating to the latter two markers is conflicting. There is also substantial evidence that therapy with clopidogrel, a specific antagonist of the platelet P2Y12 ADP-receptor, also leads to reductions in serum levels of CD40 ligand, C-reactive protein, P-selectin, and platelet—leukocyte aggregate formation. Beneficial effects of clopidogrel on inflammatory markers have been demonstrated across the spectrum of atherothrombotic disease (acute coronary syndrome patients, patients undergoing percutaneous coronary intervention (PCI), acute ischemic stroke patients, and those with peripheral arterial disease). Oral glycoprotein (GP) IIb/IIIa receptor antagonists, at doses that achieve moderate levels of receptor blockade, may paradoxically be associated with platelet-mediated pro-inflammatory effects. A similar phenomenon has been observed with intravenous GP IIb/IIIa antagonists in vitro, but most often at low doses, and data from clinical studies suggest that these agents may actually attenuate release of inflammatory mediators when administered at doses producing more complete receptor blockade.

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Section: Studies In Healthy Volunteersmentioning

confidence: 91%

Clinical evidence for anti-inflammatory effects of antiplatelet therapy in patients with atherothrombotic disease

et al. 2007

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“…This antagonism is non-competitive, irreversible, and results in 50-70% inhibition of platelet fibrinogen binding. Previous studies have demonstrated that clopidogrel reduces formation of both arterial (Hechler et al 1998) and venous (Herbert et al 1993) thrombi. Therefore, in the present study, we aimed to investigate whether clopidogrel would restore or at least decrease the harmful effects of ischemia-reperfusion via its antiaggregant effects.…”

Section: Biochemical Assaysmentioning

confidence: 96%

Protective Effects of Clopidogrel on Oxidant Damage in A Rat Model of Acute Ischemia

Kanko

Maral

Akbas

et al. 2005

Tohoku J. Exp. Med.

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Reperfusion injury is a consequence of inadequate energy supply and acidosis in ischemic tissues and a chain of events triggered by oxygen-derived free radicals released in response to exposure of oxygen. In this study, we aimed to assess the effects of clopidogrel, an antithrombotic agent, on experimental ischemia-reperfusion model in rats. The ischemia was performed by blockade of the circulation of right lower extremity at trochanter major level for 6 hours. Then, the extremity was reperfused for 4 hours. Another group of rats pretreated with clopidogrel (0.2 mg/kg/day) for 10 days prior to ischemia-reperfusion. After the reperfusion period, all rats were anesthetized with ketamine. Blood and tissue samples from the gastrocnemius muscle, liver and lungs were taken for the measurement of malondialdehyde (MDA), glutathione (GSH) levels and superoxide dismutase (SOD) activity. The results revealed that clopidogrel prevented the increase in MDA level and the decrease in GSH level and SOD activity caused by ischemia-reperfusion both in tissue samples and plasma. These findings suggest that clopidogrel is beneficial in prevention of ischemia-reperfusion injury probably via its effects on inflammatory cells, platelets, and endothelial cells.

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“…17,18 Like ticlopidine, clopidogrel is devoid of direct antiplatelet effects and must undergo hepatic metabolic modification to exhibit selective inhibition of ADP-induced platelet aggregation. 22 Clopidogrel acts by irreversibly inactivating platelet ADP receptor-initiated signaling in a dose-dependent manner.…”

mentioning

confidence: 99%

Clopidogrel Inhibition of Stent, Graft, and Vascular Thrombogenesis With Antithrombotic Enhancement by Aspirin in Nonhuman Primates

et al. 1998

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Background-A recent study showed that clopidogrel reduces thrombo-occlusive complications in patients with symptomatic atherosclerosis more effectively than aspirin. Methods and Results-The effects of clopidogrel and aspirin have been compared, singly and in combination, for measurements of 111 In-labeled platelets and 125 I-labeled fibrin deposition in baboon models of arterial thrombosis and related to platelet aggregation and expression of activation epitopes induced by ADP, collagen, and thrombin receptor agonist peptide (TRAP) and to template bleeding times (BTs). Low-dose oral clopidogrel (0.2 mg ⅐ kgIn-platelet and 125 I-fibrin deposition for segments of prosthetic vascular graft, deployed endovascular metallic stents, and endarterectomized aorta (PϽ0.009 in all cases); (2) elimination of ADP-induced platelet aggregation (PϽ0.001); (3) modest inhibition of collagen-induced platelet aggregation (PϽ0.01); (4) no reduction in TRAP-induced platelet aggregation; and (5) minimal prolongation of BTs (Pϭ0.03). High-dose oral clopidogrel (Ն2 mg/kg) produced the same effects within 3 hours. The effects of clopidogrel dissipated over 5 to 6 days. Aspirin 10 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 alone did not decrease 111 In-platelet and 125 I-fibrin deposition on segments of vascular graft but detectably decreased 111 In-platelet and 125 I-fibrin accumulation on stents (PϽ0.01), minimally inhibited ADP-and collagen-induced platelet aggregation (PϽ0.05 in both cases), and minimally prolonged BTs (Pϭ0.004). Within 3 hours of aspirin administration, the antithrombotic effects of acute high-dose or chronic low-dose clopidogrel were substantially enhanced, and BTs were modestly prolonged without inhibiting platelet aggregation induced by TRAP (PϽ0.001 in all cases compared with clopidogrel alone). Conclusions-Clopidogrel produces irreversible, dose-dependent, intermediate reduction in thrombosis that is substantially enhanced by the addition of aspirin. The effects of combining aspirin and clopidogrel need to be evaluated in patients at risk of vascular thrombosis. (Circulation. 1998;98:2461-2469.)

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Inhibitory effect of clopidogrel on platelet adhesion and intimal proliferation after arterial injury in rabbits.

Cited by 109 publications

References 32 publications

Clinical evidence for anti-inflammatory effects of antiplatelet therapy in patients with atherothrombotic disease

Clinical evidence for anti-inflammatory effects of antiplatelet therapy in patients with atherothrombotic disease

Protective Effects of Clopidogrel on Oxidant Damage in A Rat Model of Acute Ischemia

Clopidogrel Inhibition of Stent, Graft, and Vascular Thrombogenesis With Antithrombotic Enhancement by Aspirin in Nonhuman Primates

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