PB0509 - Dual Antiplatelet Therapy Is Associated With High α-Tubulin Acetylation in Platelets From Coronary Artery Disease Patients

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Valentine Robaux, Master 120

PhD student
UCLouvain
Brussels, Brussels Hoofdstedelijk Gewest, Belgium

Co-Author(s)

SK

Shakeel Kautbally

Doctor of Medicine
Cliniques Universitaires Saint-Luc
Brussels, Brussels Hoofdstedelijk Gewest, Belgium
AG

Audrey Ginion

Research Assistant
UCLouvain
Brussels, Brussels Hoofdstedelijk Gewest, Belgium
MD

Mélanie Dechamp

Doctor and PhD student
Cliniques Universitaires Saint-Luc and UCLouvain
Brussels, Brussels Hoofdstedelijk Gewest, Belgium
SL

Sibille Lejeune

PhD student
Cliniques Universitaires Saint-Luc
Brussels, Brussels Hoofdstedelijk Gewest, Belgium
LB

Luc Bertrand

Maitre de recherche FNRS
UCLouvain
Brussels, Brussels Hoofdstedelijk Gewest, Belgium
SH

Sandrine Horman

Professor
Pôle de Recherche Cardiovasculaire (CARD), IREC, UCLouvain, Brussels, Belgium
Brussels, Brussels Hoofdstedelijk Gewest, Belgium
CB

Christophe Beauloye

Principal Investigator
UCLouvain and Cliniques Universitaires Saint-Luc
Brussels, Brussels Hoofdstedelijk Gewest, Belgium

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.