Abstract Body (Do not enter title and authors here): Introduction: Platelets play a central role in the pathophysiology of myocardial infarction (MI), including thrombosis and inflammation. Nonetheless, few studies have used unbiased transcriptomics to characterize platelets at the time of an MI. Further, the relationship between platelet phenotype and MI subtype is uncertain.
Aim: To investigate the platelet transcriptome during acute MI and by MI subtype (MI with obstructive coronary artery disease (MI-CAD) or with no obstructive coronary arteries (MINOCA).
Methods: Platelet RNA-sequencing was performed in females referred for invasive coronary angiography for MI (n=40), or for evaluation of stable angina (n=38). MI cases were categorized into either MI-CAD or MINOCA according to the presence or absence of a ≥50% diameter stenosis in ≥1 major epicardial coronary artery.
Results: Among females with MI (47.5% MI-CAD, 52.5% MINOCA), the median age was 63 years, 70% were white, 45% Hispanic, and co-morbidities including hypertension (45%), diabetes (22.5%), and dyslipidemia (60%) were common. There were no differences in age, race, ethnicity, BMI, hypertension, diabetes, or dyslipidemia between participants with MI and those with stable angina. In total, 1421 genes were differentially expressed (p<0.05), with 657 up- and 764 downregulated platelet transcripts in MI relative to stable angina. By ingenuity pathway analysis, canonical pathways associated with actin cytoskeleton, integrin, interferon signaling, and mitochondrial dysfunction were positively enriched in MI platelets, and oxidative phosphorylation and RHOGDI signaling were negatively enriched. When stratified by MI subtype, 531 genes (p<0.05) were differentially expressed (334-up, 197-downregulated) in MI-CAD vs MINOCA. MI-CAD platelets were positively enriched in genes in canonical pathways associated with neutrophil degranulation, neutrophil extracellular traps, and atherosclerosis signaling versus MINOCA. Among all patients with MI, unbiased clustering analysis classified participants into 3 distinct groups that differed in composition by clinical MI subtype (group A – 100% MINOCA, B – 80% MINOCA, and C – 0% MINOCA, P<0.001).
Conclusions: The platelet transcriptome is enriched in transcripts linked to classical platelet activation responses (actin cytoskeleton, integrin, interferon signaling, and mitochondrial dysfunction) in the setting of MI. Among individuals with MI, platelet RNA sequencing discriminated individuals with MI-CAD versus MINOCA.