Abstract
Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression model used to combine the gene expression in a STEMI vs healthy donors score showed an AUC of 0.95. The same five differentially expressed genes were externally validated using platelet gene expression data from patients with coronary atherosclerosis but without thrombosis. Platelet gene expression profile highlights five genes able to identify STEMI patients and to discriminate them in the background of atherosclerosis. Consequently, early signals of an imminent acute myocardial infarction are likely to be found by platelet gene expression profiling before the infarction occurs.
Highlights
Acute myocardial infarction is a sudden event that is fatal in approximately one-third of patients, with about half of the deaths occurring within one hour
The gene that showed the strongest evidence of differential expression between the ST-segment elevation myocardial infarction (STEMI) and healthy donors (HD) groups (Table 1) was FKBP5, followed by S100P, SAMSN1, S100A12 and CLEC4E (Fig. 1, panel a and Supplemental Table 1)
It is worth noting that all 5 differentially expressed genes (DEGs) were already known to be associated with cardiovascular conditions: S100A12 with coronary artery disease (CAD) and atherosclerotic plaques[24]; FKBP5 with STEMI25; CLEC4E and SAMSN1 with atherosclerotic lesions[26,27]; and S100P with acute coronary syndrome (ACS)[23] (Table 2)
Summary
Acute myocardial infarction is a sudden event that is fatal in approximately one-third of patients, with about half of the deaths occurring within one hour. It is frequently attributed to coronary atherosclerotic plaque rupture and the consequent exposure of thrombogenic substances that promote platelet activation/aggregation, the activation of coagulation and, the formation of an intraluminal thrombus that limits coronary blood flow[1,2]. Autopsy data show that a sizable proportion of the subjects who die suddenly of non-cardiac causes have fissured plaques without thrombosis in their coronary arteries[3]. The rupture of coronary atherosclerotic plaque is much more frequent than thrombus formation. It has been suggested that individual reactivity to plaque rupture may play a causative role in provoking the clinical event of acute myocardial infarction[4,5,6,7,8]. This study was designed to test the hypothesis that platelet transcriptome contains the gene signature of an imminent myocardial infarction
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