Platelet transcriptome profile of acute myocardial infarction

Acute myocardial infarction (AMI) is a sudden event commonly attributed to coronary atherosclerotic plaque rupture with subsequent exposure of thrombogenic substances that promote platelet activation/aggregation as well as coagulation activation and, ultimately, intraluminal thrombus formation thus limiting coronary blood flow. Although plaque rupture or fissuring frequently occurs in atherosclerosis, only a small proportion of ruptured plaques develops thromboses. It has been suggested that individual reactivity to plaque rupture may have a causative role in provoking the clinical event of AMI. Platelets contribute to the genesis and progression of atherosclerosis and to the precipitation of the atherothrombotic event after plaque rupture. Platelets are anucleate cells formed from the cytoplasm of megakaryocytes and circulate in the blood stream for about 7-10 days. Since platelets are without nucleus, they retain megakaryocytes†"derived mRNAs that are unique in representing a nearly fixed transcriptome. The present study was designed to test whether platelets transcriptome may predate the development of a future myocardial infarction. The abundance of platelets transcripts levels were measured using Human Transcriptome Array 2.0 (Affymetrix). Bioinformatics analyses were conducted to identify the differentially expressed genes (p.value ? 0.05, fold-change ? ± 1.5) between patients with ST elevation myocardial infarction (STEMI, n=20), stable coronary artery disease (sCAD, n=20) and healthy donors (HD, n=20). REACTOME and DAVID analyses were performed respectively to identify pathways and biological processes associated with lists of differentially expressed genes (DEGs). A total of 149 DEGs were observed comparing sCAD patients and HD platelet trascriptome. MNF2 and PRKCD were identified as the most up-regulated genes and CXCL8 as the most down-regulated. A number of 76 DEGs were detected in STEMI subjects compared with HD. S100A12 and CLEC4E, in STEMI patients, resulted the highest up-regulated mRNAs while CXCL8 was the most down-regulated followed by SNORD13, SNORD117 and RMRP. The comparison between STEMI and sCAD subjects allowed the identification of 138 de-regulated genes. S100A12 was again the most up-regulated gene in STEMI. From this preliminary analysis, we observed the presence of distinctive gene-expression patterns for sCAD and STEMI. These results suggested the possibility to find a more specific gene-set for STEMI condition. Thus, we focused on the characterization of a gene-signature able to discriminate patients with myocardial infarction and eventually we identified a STEMI signature consisting of 38 genes from these analyses. In conclusion, our preliminary results show that variations in gene expression profile of megakaryocytes may occur before of an AMI and that platelet transcriptome could act as a fingerprint indicating the development of a future myocardial infarction.