Dual Antiplatelet Therapy Is Associated With High α-Tubulin Acetylation in Platelets From Coronary Artery Disease Patients

V. Robaux¹, S. Kautbally², A. Ginion¹, M. Dechamp³, S. Lejeune², L. Bertrand¹, S. Horman⁴, C. Beauloye⁵

¹UCLouvain, Brussels, Brussels Hoofdstedelijk Gewest, Belgium, ²Cliniques Universitaires Saint-Luc, Brussels, Brussels Hoofdstedelijk Gewest, Belgium, ³Cliniques Universitaires Saint-Luc and UCLouvain, Brussels, Brussels Hoofdstedelijk Gewest, Belgium, ⁴Université catholique de louvain, Louvain-La-Neuve, Brabant Wallon, Belgium, ⁵UCLouvain and Cliniques Universitaires Saint-Luc, Brussels, Brussels Hoofdstedelijk Gewest, Belgium

Abstract Number: PB0509

Meeting: ISTH 2022 Congress

Theme: Arterial Thromboembolism » Cardiovascular Risk Factors

Background: Platelet inhibition is the main treatment strategy to prevent atherothrombosis. Despite dual antiplatelet therapy (DAPT) combining aspirin and a P2Y12 receptor inhibitor, high platelet reactivity persists in some patients due to poor response to treatment and is associated with ischemic risk. It remains unknown if circulating platelets in high-risk patients have different morphological characteristics which could participate in their pro-thrombotic potential.

Aims: We postulated that α-tubulin acetylation, a cytoskeletal modification known to regulate platelet shape change, could reflect circulating platelet reactivity and impact their morphology.

Methods: We collected arterial blood samples from 187 patients admitted for coronary angiography. Platelet reactivity was assessed in whole blood using multiplate analysis. Platelets were then isolated to evaluate α-tubulin acetylation level by western blotting.

141 patients were taking aspirin among which 32 were treated with an additional P2Y12 inhibitor. DAPT didn’t achieve sufficient platelet inhibition in 8 out of 32 patients.

Participants provided written informed consent and the study was approved by the institutional ethics committee.

Results: Platelet α-tubulin acetylation was significantly increased in DAPT-treated patients (p < 0.001). A minority of non-treated patients (11.4%) exhibited high α-tubulin acetylation (third acetyl α-tubulin tertile) whereas a high level was observed in most patients on efficient DAPT (83.3%). Interestingly, the proportion of patients with high acetyl α-tubulin (37.5%) level was drastically decreased in clopidogrel non-responders. Multivariate logistic regression further supported that efficient DAPT is independently associated with a 27-fold increase in the likelihood of being in the highest acetyl α-tubulin tertile (p < 0.001).

Conclusion(s): We revealed high platelet α-tubulin acetylation as a potential marker of efficient platelet inhibition by dual antiplatelet therapy. Since α-tubulin acetylation is a hallmark of stable microtubules, its increase could contribute to maintaining resting morphology of circulating platelets.

To cite this abstract in AMA style:

Robaux V, Kautbally S, Ginion A, Dechamp M, Lejeune S, Bertrand L, Horman S, Beauloye C. Dual Antiplatelet Therapy Is Associated With High α-Tubulin Acetylation in Platelets From Coronary Artery Disease Patients [abstract]. https://abstracts.isth.org/abstract/dual-antiplatelet-therapy-is-associated-with-high-%ce%b1-tubulin-acetylation-in-platelets-from-coronary-artery-disease-patients/. Accessed September 24, 2023.

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