Inhibition of Arginine Methylation Impairs Platelet Function

Area of Science:

• Biochemistry
• Hematology
• Pharmacology

Background:

• Protein arginine methyltransferases (PRMTs) are enzymes catalyzing arginine methylation.
• PRMT inhibitors are developed as anti-cancer agents with oral administration.
• Potential off-target effects of PRMT inhibitors on platelets are unknown.

Purpose of the Study:

• Investigate the role of arginine methylation in platelets.
• Assess the impact of PRMT inhibitors on platelet function and receptor expression.

Main Methods:

• Incubation of human platelets with PRMT inhibitors.
• Measurement of platelet aggregation in response to agonists.
• Analysis of platelet integrin α_IIbβ₃ membrane expression and activation.

Main Results:

• Key platelet proteins are modified by arginine methylation.
• PRMT inhibitors impair platelet aggregation with IC₅₀ values in the microM range.
• PRMT inhibitors decrease membrane expression and activation of integrin α_IIbβ₃.

Conclusions:

• Arginine methylation is relevant in platelet function.
• PRMT inhibitors exhibit antiplatelet activity.
• PRMT inhibitors may be repurposed as antiplatelet drugs, and clinical trials should monitor for adverse effects on platelets.