The effect of clopidogrel on platelet activity in patients with and without type-2 diabetes mellitus: a comparative study

Schuette, Claudia; Steffens, Daniel; Witkowski, Marco; Stellbaum, Caroline; Bobbert, Peter; Schultheiss, Heinz‐Peter; Rauch, Ursula

doi:10.1186/s12933-015-0182-7

Cited by 43 publications

(38 citation statements)

References 41 publications

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“…Under diabetic conditions, chronic inflammatory signaling in the vasculature sustains endothelial dysfunction, leukocyte infiltration, and a pro-thrombotic environment [1,2].…”

Section: Introductionmentioning

confidence: 99%

Vascular miR-181b controls tissue factor-dependent thrombogenicity and inflammation in type 2 diabetes

Witkowski

Saffarzadeh

et al. 2020

Cardiovasc Diabetol

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Background: Diabetes mellitus is characterized by chronic vascular inflammation leading to pathological expression of the thrombogenic full length (fl) tissue factor (TF) and its isoform alternatively-spliced (as) TF. Blood-borne TF promotes factor (F) Xa generation resulting in a pro-thrombotic state and cardiovascular complications. MicroRNA (miR)s impact gene expression on the post-transcriptional level and contribute to vascular homeostasis. Their distinct role in the control of the diabetes-related procoagulant state remains poorly understood. Methods: In a cohort of patients with poorly controlled type 2 diabetes (n = 46) plasma levels of miR-181b were correlated with TF pathway activity and markers for vascular inflammation. In vitro, human microvascular endothelial cells (HMEC)-1 and human monocytes (THP-1) were transfected with miR-181b or anti-miR-181b and exposed to tumor necrosis factor (TNF) α or lipopolysaccharides (LPS). Expression of TF isoforms, vascular adhesion molecule (VCAM) 1 and nuclear factor (NF) κB nuclear translocation was assessed. Moreover, aortas, spleen, plasma, and bone marrowderived macrophage (BMDM)s of mice carrying a deletion of the first miR-181b locus were analyzed with respect to TF expression and activity. Results: In patients with type 2 diabetes, plasma miR-181b negatively correlated with the procoagulant state as evidenced by TF protein, TF activity, d-dimer levels as well as markers for vascular inflammation. In HMEC-1, miR-181b abrogated TNFα-induced expression of flTF, asTF, and VCAM1. These results were validated using the anti-miR-181b. Mechanistically, we confirmed a miR-181b-mediated inhibition of importin-α3 (KPNA4) leading to reduced nuclear translocation of the TF transcription factor NFκB. In THP-1, miR-181b reduced both TF isoforms and FXa generation in response to LPS due to targeting phosphatase and tensin homolog (PTEN), a principal inducer for TF in monocytes. Moreover, in miR-181−/− animals, we found that reduced levels of miR-181b were accompanied by increased TF, VCAM1, and KPNA4 expression in aortic tissue as well as increased TF and PTEN expression in spleen. Finally, BMDMs of miR-181−/− mice showed increased TF expression and FXa generation upon stimulation with LPS. Conclusions: miR-181b epigenetically controls the procoagulant state in diabetes. Reduced miR-181b levels contribute to increased thrombogenicity and may help to identify individuals at particular risk for thrombosis.

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“…Under diabetic conditions, chronic inflammatory signaling in the vasculature sustains endothelial dysfunction, leukocyte infiltration, and a pro-thrombotic environment [1,2].…”

Section: Introductionmentioning

confidence: 99%

Vascular miR-181b controls tissue factor-dependent thrombogenicity and inflammation in type 2 diabetes

Witkowski

Saffarzadeh

et al. 2020

Cardiovasc Diabetol

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“…These interesting findings could be partially explained by the fact that increased platelet reactivity was more likely seen in DM [4] and increased aspirin resistance in the elderly [5]. Following a sensitivity http://dx.…”

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confidence: 99%

The impact of dual antiplatelet therapy duration on primary composite endpoint after drug-eluting stent implantation: A meta-analysis of 10 randomized trials

Pang

Shi

Zhang

et al. 2016

International Journal of Cardiology

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“…Also in this study, as shown in table 2, difference of aggregation after dual antiplatelet therapy administration (∆t1-t2) is higher in non diabetic group than in diabetic group (3.30±2.91 vs 6.83±5.97, p=0.103). As mentioned in another research, diabetes mellitus can lead to platelet hyperreactivity (increased adhesion, activation, aggregation, and platelet turnover) (Ferreiro et al, 2011;Schuette et al, 2015). Thus, some researcher or clinician sometimes increase the maintenance dose of dual antiplatelet (Angiolillo et al, 2007;DiChiara et al, 2007), or used triple antiplatelet as maintenance dose after PCI (Lee et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

The Effect of Dual Antiplatelet Post Percutaneous Coronary Intervention On Aggregation of Platelet In Myocardial Infarction Patients With Diabetes Mellitus and Non Diabetes Mellitus

Rahmawati

Yogiarto

Zulkarnaen

2018

Indonesian J. Pharm.

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To analyze the differences in the effect of dual antiplatelet post PCI on the percentage of aggregation in myocardial infarction patients with DM and non DM. Percentage of aggregation were analyzed using light transmission aggregometry (LTA) before loading dose, after PCI, and after maintenance dose of dual antiplatelet (aspirin 100mg and clopidogrel 75mg). Total 22 patients were participated in this study divided into 10 and 12 patients in diabetic and non diabetic group. Percentage of aggregation after taking dual antiplatelet maintenace dose decrease significantly in both group (p=0.006 in diabetic group and p=0.002 in non diabetic group). Mean reduction of percentage of aggregation in diabetic group (3.30±2.91%) is less than non diabetic group (6.83±5.97%). Statistical analysis shows that the mean reduction of percentage of aggregation between two groups were not significantly different (p>0.05). Mean percentage of aggregation after dual antiplatelet maintenance dose was higher in diabetic group and mean reduction of percentage of aggregation was higher in non diabetic group, although statistically in both group it is not significantly different.

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The effect of clopidogrel on platelet activity in patients with and without type-2 diabetes mellitus: a comparative study

Cited by 43 publications

References 41 publications

Vascular miR-181b controls tissue factor-dependent thrombogenicity and inflammation in type 2 diabetes

Vascular miR-181b controls tissue factor-dependent thrombogenicity and inflammation in type 2 diabetes

The impact of dual antiplatelet therapy duration on primary composite endpoint after drug-eluting stent implantation: A meta-analysis of 10 randomized trials

The Effect of Dual Antiplatelet Post Percutaneous Coronary Intervention On Aggregation of Platelet In Myocardial Infarction Patients With Diabetes Mellitus and Non Diabetes Mellitus

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