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Your search keyword '"Warner, Timothy A."' showing total 28 results
Start Over Author "Warner, Timothy A." Publisher lippincott williams & wilkins
28 results on '"Warner, Timothy A."'

1. Neutrophil-Derived Protein S100A8/A9 Alters the Platelet Proteome in Acute Myocardial Infarction and Is Associated With Changes in Platelet Reactivity.

Author

Joshi, Abhishek, Schmidt, Lukas E., Burnap, Sean A., Lu, Ruifang, Chan, Melissa V., Armstrong, Paul C., Baig, Ferheen, Gutmann, Clemens, Willeit, Peter, Santer, Peter, Barwari, Temo, Theofilatos, Konstantinos, Kiechl, Stefan, Willeit, Johann, Warner, Timothy D., Mathur, Anthony, and Mayr, Manuel

Published
2022
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2. Newly Formed Reticulated Platelets Undermine Pharmacokinetically Short-Lived Antiplatelet Therapies

Author

Armstrong, Paul C., Hoefer, Thomas, Knowles, Rebecca B., Tucker, Arthur T., Hayman, Melissa A., Ferreira, Plinio M., Chan, Melissa V., and Warner, Timothy D.

Subjects
Adult, Blood Platelets, Male, Ticagrelor, Adenosine, Adolescent, Platelet Aggregation, Platelet Function Tests, Thienopyridines, aspirin, Coronary Artery Disease, Thrombopoiesis, Young Adult, Translational Sciences, Humans, thrombosis, Aged, Aged, 80 and over, Middle Aged, Case-Control Studies, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Purinergic P2Y Receptor Antagonists, Drug Therapy, Combination, Platelet Aggregation Inhibitors, Half-Life
Abstract

Supplemental Digital Content is available in the text., Objective— Aspirin together with thienopyridine P2Y12 inhibitors, commonly clopidogrel, is a cornerstone of antiplatelet therapy. However, many patients receiving this therapy display high on-treatment platelet reactivity, which is a major therapeutic hurdle to the prevention of recurrent thrombotic events. The emergence of uninhibited platelets after thrombopoiesis has been proposed as a contributing factor to high on-treatment platelet reactivity. Here, we investigate the influences of platelet turnover on platelet aggregation in the face of different dual-antiplatelet therapy strategies. Approach and Results— Traditional light transmission aggregometry, cytometry, advanced flow cytometric imaging, and confocal microscopy were used to follow the interactions of populations of platelets from healthy volunteers and patients with stable cardiovascular disease. Newly formed, reticulated platelets overproportionately contributed to, and clustered at, the core of forming aggregates. This phenomenon was particularly observed in samples from patients treated with aspirin plus a thienopyridine, but was absent in samples taken from patients treated with aspirin plus ticagrelor. Conclusions— Reticulated platelets are more reactive than older platelets and act as seeds for the formation of platelet aggregates even in the presence of antiplatelet therapy. This is coherent with the emergence of an uninhibited subpopulation of reticulated platelets during treatment with aspirin plus thienopyridine, explained by the short pharmacokinetic half-lives of these drugs. This phenomenon is absent during treatment with ticagrelor, because of its longer half-life and ability to act as a circulating inhibitor. These data highlight the important influences of pharmacokinetics on antiplatelet drug efficacies, especially in diseases associated with increased platelet turnover.

Published
2017

3. Evidence That Links Loss of Cyclooxygenase-2 With Increased Asymmetric Dimethylarginine

Author

Ahmetaj-Shala, Blerina, Kirkby, Nicholas S., Knowles, Rebecca, Al’Yamani, Malak, Mazi, Sarah, Wang, Zhen, Tucker, Arthur T., Mackenzie, Louise, Armstrong, Paul C. J., Nüsing, Rolf M., Tomlinson, James A. P., Warner, Timothy D., Leiper, James, and Mitchell, Jane A.

Subjects
prostaglandins, kidney, endothelium, nitric oxide, Hypertension, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Original Articles, pharmacology
Abstract

Supplemental Digital Content is available in the text., Background— Cardiovascular side effects associated with cyclooxygenase-2 inhibitor drugs dominate clinical concern. Cyclooxygenase-2 is expressed in the renal medulla where inhibition causes fluid retention and increased blood pressure. However, the mechanisms linking cyclooxygenase-2 inhibition and cardiovascular events are unknown and no biomarkers have been identified. Methods and Results— Transcriptome analysis of wild-type and cyclooxygenase-2−/− mouse tissues revealed 1 gene altered in the heart and aorta, but >1000 genes altered in the renal medulla, including those regulating the endogenous nitric oxide synthase inhibitors asymmetrical dimethylarginine (ADMA) and monomethyl-l-arginine. Cyclo-oxygenase-2−/− mice had increased plasma levels of ADMA and monomethyl-l-arginine and reduced endothelial nitric oxide responses. These genes and methylarginines were not similarly altered in mice lacking prostacyclin receptors. Wild-type mice or human volunteers taking cyclooxygenase-2 inhibitors also showed increased plasma ADMA. Endothelial nitric oxide is cardio-protective, reducing thrombosis and atherosclerosis. Consequently, increased ADMA is associated with cardiovascular disease. Thus, our study identifies ADMA as a biomarker and mechanistic bridge between renal cyclooxygenase-2 inhibition and systemic vascular dysfunction with nonsteroidal anti-inflammatory drug usage. Conclusions— We identify the endogenous endothelial nitric oxide synthase inhibitor ADMA as a biomarker and mechanistic bridge between renal cyclooxygenase-2 inhibition and systemic vascular dysfunction.

Published
2015

8. Association of MicroRNAs and YRNAs With Platelet Function.

Author

Kaudewitz, Dorothee, Skroblin, Philipp, Bender, Lukas H., Barwari, Temo, Willeit, Peter, Pechlaner, Raimund, Sunderland, Nicholas P., Willeit, Karin, Morton, Allison C., Armstrong, Paul C., Melissa V. Chan, Ruifang Lu, Xiaoke Yin, Gracio, Filipe, Dudek, Katarzyna, Langley, Sarah R., Zampetaki, Anna, Rinaldis, Emanuele de, Shu Ye, and Warner, Timothy D.

Published
2016
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28. Reply to letter regarding article, "evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethylarginine: novel explanation of cardiovascular side effects associated with anti-inflammatory drugs".

Author

Ahmetaj-Shala, Blerina, Kirkby, Nicholas S., Knowles, Rebecca, Al'Yamani, Malak, Mazi, Sara, Zhen Wang, Tucker, Arthur T., Mackenzie, Louise S., Armstrong, Paul C. J., Nüsing, Rolf M., Tomlinson, James A. P., Warner, Timothy D., Leiper, James, Mitchell, Jane A., and Wang, Zhen

Published
2015
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