Abstract Number: OC 10.3
Meeting: ISTH 2021 Congress
Theme: Platelets and Megakaryocytes » Platelet Proteomics and Genomics
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. 
HSPA5 upregulation in bad (third tertile) vs. good (first tertile) ASA responders in patients with cardiovascular disease.
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.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-proteome-and-variability-in-the-responsiveness-to-low-dose-aspirin-in-patients-with-cardiovascular-disease/