Dual antiplatelet therapy is associated with high α-tubulin acetylation in circulating platelets from coronary artery disease patients
(2023) Platelets (London) — Vol. 34, n° 1, p. 2250002 [1-11] (2023)
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- Platelet inhibition is the main treatment strategy to prevent atherothrombotic complications after acute coronary syndrome or percutaneous coronary intervention. Despite dual antiplatelet therapy (DAPT) combining aspirin and a P2Y12 receptor inhibitor, high on-treatment platelet reactivity (HPR) persists in some patients due to poor response to treatment and is associated with ischemic risk. Tubulin acetylation has been pointed out as a hallmark of stable microtubules responsible for the discoid shape of resting platelets. However, the impact of antiplatelet treatments on this post-translational modification has never been studied. This study investigated whether tubulin acetylation differs according to antiplatelet therapy and on-treatment platelet reactivity. Platelets were isolated from arterial blood samples of 241 patients admitted for coronary angiography, and levels of α-tubulin acetylation on lysine 40 (α-tubulin K40 acetylation) were assessed by western blot. We show that platelet α-tubulin K40 acetylation was significantly increased in DAPT-treated patients. In addition, the proportion of patients with high levels of α-tubulin K40 acetylation was drastically reduced among DAPT-treated patients with HPR. Multivariate logistic regression confirmed that DAPT resulting in adequate platelet inhibition was strongly associated with elevated α-tubulin K40 acetylation. In conclusion, our study highlights the role of elevated platelet α-tubulin K40 acetylation as a marker of platelet inhibition in response to DAPT. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov - NCT03034148.
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Robaux, V., Kautbally, S., Ginion, A., Dechamps, M., Lejeune, S., Menghoum, N., Bertrand, L., Pouleur, A.-C., Horman, S., & Beauloye, C. (2023). Dual antiplatelet therapy is associated with high α-tubulin acetylation in circulating platelets from coronary artery disease patients. Platelets (London), 34(1), 2250002 [1-11]. https://doi.org/10.1080/09537104.2023.2250002 (Original work published 2023)