Reduced Variability to Aspirin Antiplatelet Effect by the Coadministration of Statins in High‐Risk Patients for Cardiovascular Disease

Tacconelli, Stefania; Dovizio, Melania; Francesco, Luigia Di; Meneguzzi, Alessandra; D’Agostino, Ilaria; Evangelista, Virgilio; Manarini, Stefano; Capone, Marta L.; Grossi, L.; Porreca, Ettore; Febbo, Concetta Di; Bruno, Annalisa; Ballerini, Patrizia; Levantesi, Giacomo; Fava, Cristiano; Minuz, Pietro; Patrignani, Paola

doi:10.1002/cpt.1075

Cited by 7 publications

(12 citation statements)

References 41 publications

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“…11 Importantly, increased expression of MRP4 in platelets contributes to HARPR. [12][13][14] Overall, these findings suggest a 'platelet adaptation' process in response to chronic treatment with aspirin, which originates in megakaryocytes and leads to recovery of platelet function. 15 Adenosine diphosphate (ADP) is one of the major platelet agonists and plays a key role in shape changes and platelet aggregation via purinergic receptors.…”

Section: Introductionmentioning

confidence: 81%

Aspirin-Dependent Effects on Purinergic P2Y1 Receptor Expression

et al. 2019

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Chronic treatment with aspirin in healthy volunteers (HVs) is associated with recovery of adenosine diphosphate (ADP)-induced platelet activation. The purinergic P2Y1 receptor exerts its effects via a Gq-protein, which is the same biochemical pathway activated by thromboxane-A2 receptor. We hypothesized that recovery of ADP-induced platelet activation could be attributed to increased P2Y1 expression induced by chronic aspirin exposure. We performed a multi-phase investigation which embraced both in vitro and in vivo experiments conducted in (1) human megakaryoblastic DAMI cells, (2) human megakaryocytic progenitor cell cultures, (3) platelets obtained from HVs treated with aspirin and (4) platelets obtained from aspirin-treated patients. DAMI cells treated with aspirin or WY14643 (PPARα agonist) had a significant up-regulation of P2Y1 mRNA, which was shown to be a PPARα-dependent process. In human megakaryocytic progenitors, in the presence of aspirin or WY14643, P2Y1 mRNA expression was higher than in mock culture. P2Y1 expression increased in platelets obtained from HVs treated with aspirin for 8 weeks. Platelets obtained from patients who were on aspirin for more than 2 months had increased P2Y1 expression and ADP-induced aggregation compared with patients on aspirin treatment for less than a month. Overall, our results suggest that aspirin induces genomic changes in megakaryocytes leading to P2Y1 up-regulation and that PPARα is the nuclear receptor involved in this regulation. Since P2Y1 is coupled to the same Gq-protein of thromboxane-A2 receptor, platelet adaptation in response to pharmacological inhibition seems not to be receptor specific, but may involve other receptors with the same biochemical pathway.

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Section: Introductionmentioning

confidence: 81%

Aspirin-Dependent Effects on Purinergic P2Y1 Receptor Expression

et al. 2019

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“…Furthermore, the effectiveness of medicines can also be influenced by comedication. A recent study shows that coadministration of low-dose aspirin and atorvastatin, and possibly other statins, reduces cardiovascular events (35). Still, an important role may be reserved for using the circadian rhythm for drug treatment, such as with acetylsalicylic acid.…”

Section: Blood Clotting and Circadian Rhythmmentioning

confidence: 99%

Circadian Rhythm of Cardiovascular Disease: The Potential of Chronotherapy With Aspirin

Buurma

Diemen

Thijs

et al. 2019

Front. Cardiovasc. Med.

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Almost all the systems in our body adhere to a daily 24 h rhythm. The cardiovascular system is also affected by this 24 h rhythm. In the morning there is a change in various cardiovascular processes, including platelet aggregability. These changes may play a role in the relative excess of early morning cardiovascular events. The number of recurrent cardiovascular diseases (CVD) could, in theory, be reduced by responding to this 24 h rhythm with timed medication intake (chronotherapy), which also applies to aspirin. Multiple studies on chronotherapy with low-dose aspirin are promising, showing a decrease in early morning platelet activity with evening intake compared with morning intake. However, in order to further demonstrate its clinical impact, randomized trials with cardiovascular events as a primary outcome are needed. This review discusses the available evidence of the effects of circadian rhythm on CVD and the potential positive effect of chronotherapy with aspirin.

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“…Aspirin (acetylsalicylic acid) is a non-steroidal anti-inflammatory drug (NSAID, has anti-inflammatory and anti-thrombotic effects used in the treatment of various inflammatory disorders [157] . Aspirin inhibits PGs synthesis and causes irreversible acetylation of platelets COX with suppression of thromboxane A2 leading to a noteworthy antiplatelet effect [158] . Furthermore, different studies showed that aspirin inhibits NETosis and platelet activations and NETs formation [159] .…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality

Al-Kuraishy

Al-Gareeb

Al-Hussaniy³

et al. 2022

International Immunopharmacology

137

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Coronavirus disease 2019 (Covid-19) is a worldwide infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) . In severe SARS-CoV-2 infection, there are severe inflammatory reactions due to neutrophil recruitments and infiltration in the different organs with the formation of neutrophil extracellular traps (NETs), which involved various complications of SARS-CoV-2 infection . Therefore, the objective of the present review was to explore the potential role of NETs in the pathogenesis of SARS-CoV-2 infection and to identify the targeting drugs against NETs in Covid-19 patients. Different enzyme types are involved in the formation of NETs, such as neutrophil elastase (NE), which degrades nuclear protein and release histones, peptidyl arginine deiminase type 4 (PADA4), which releases chromosomal DNA and gasdermin D, which creates pores in the NTs cell membrane that facilitating expulsion of NT contents. Despite of the beneficial effects of NETs in controlling of invading pathogens, sustained formations of NETs during respiratory viral infections are associated with collateral tissue injury. Excessive development of NETs in SARS-CoV-2 infection is linked with the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) due to creation of the NETs-IL-1β loop. Also, aberrant NTs activation alone or through NETs formation may augment SARS-CoV-2-induced cytokine storm (CS) and macrophage activation syndrome (MAS) in patients with severe Covid-19. Furthermore, NETs formation in SARS-CoV-2 infection is associated with immuno-thrombosis and the development of ALI/ARDS. Therefore, anti-NETs therapy of natural or synthetic sources may mitigate SARS-CoV-2 infection-induced exaggerated immune response, hyperinflammation, immuno-thrombosis, and other complications.

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Reduced Variability to Aspirin Antiplatelet Effect by the Coadministration of Statins in High‐Risk Patients for Cardiovascular Disease

Cited by 7 publications

References 41 publications

Aspirin-Dependent Effects on Purinergic P2Y1 Receptor Expression

Aspirin-Dependent Effects on Purinergic P2Y1 Receptor Expression

Circadian Rhythm of Cardiovascular Disease: The Potential of Chronotherapy With Aspirin

Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality

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