Abstract Number: OC 10.3
Meeting: ISTH 2021 Congress
Background: Platelet (PLT) activation plays a key role in atherothrombosis, and low-dose aspirin (ASA) represents the cornerstone for cardiovascular (CV) prevention. ASA, which induces a permanent inactivation of PLT cyclooxygenase (COX)-1, can be less effective in patient at CV risk. Metabolic abnormalities, associated with CV disease, may affect PLT proteome and relative ASA response.
Aims: To characterize the PLT protein pathways associated with a less-than-expected ASA response.
Methods: Two-hundred patients on chronic ASA treatment (100 mg/day) were enrolled. Blood sampling was performed at 10 hours and 24 hours after a witnessed ASA administration. Patients were stratified in tertiles according to serum TXB2 (ex vivo index of COX-1-dependent TXA2 production) slope. First and third tertiles (good responders vs. bad responders) were compared. To study the proteomic profile of isolated PLT, a label free proteomic analysis was performed on a pool of 20 patients for each clinical group. Resulting differentially-expressed proteins were validated by western blot (WB). Each subject signed written informed consent. Protocol was approved (GR-2011-02350450).
Results: Comparing bad responders vs. good responders, reactive oxygen species production was the biological process predicted to be differentially expressed by the proteomic analysis. Consistent with this analysis, WB revealed a significant up-regulation of heat shock protein A5 (HSPA5) (p-value= 0.0098) in third vs. first tertile (Fig.1). HSPA5 controls the PLT cell faith, by triggering adaptative pathways in response to oxidative stress onset.
Conclusions: Proteomic comparison of PLT proteins in bad (third tertile) vs. good (first tertile) ASA responders has highlighted that oxidative stress plays a pivotal role in the recovery of COX-1 activity.
To cite this abstract in AMA style:Ciotti S, Simeone PG, Liani R, Tripaldi R, Boccatonda A, D'Ardes D, Recchiuti A, Romano M, Santilli F. Platelet Proteome and Variability in the Responsiveness to Low-dose Aspirin in Patients with Cardiovascular Disease [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/platelet-proteome-and-variability-in-the-responsiveness-to-low-dose-aspirin-in-patients-with-cardiovascular-disease/. Accessed October 2, 2023.
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