Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c.

Area of Science:

• Hematology
• Genomics
• Pharmacology

Background:

• Atherothrombosis pathophysiology shows poorly understood racial differences.
• Platelet function and transcriptome variations across races require investigation.

Purpose of the Study:

• To explore racial differences in platelet function and transcriptome.
• To investigate the role of PAR4 thrombin receptor in racial disparities of platelet activation.

Main Methods:

• Compared platelet aggregation and calcium mobilization in healthy Black and White subjects.
• Analyzed RNA and protein expression, including PCTP and miR-376c.
• Assessed the impact of PC-TP inhibition on platelet activation.

Main Results:

• Black subjects exhibited greater PAR4-mediated platelet activation.
• PCTP (phosphatidylcholine transfer protein) levels were higher in Black subjects and linked to PAR4 reactivity.
• miR-376c levels were inversely correlated with PCTP and PAR4 reactivity, with differential expression linked to the DLK1-DIO3 locus.

Conclusions:

• PC-TP contributes to racial differences in PAR4-mediated platelet activation.
• Genomic factors influence platelet function differently across races.
• Race must be considered in anti-thrombotic drug development.