Sighting acute myocardial infarction through platelet gene expression

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.

Figure 1

Gene expression values of the five identified genes. Panel a: Individual gene expression values in STEMI patients (red), and healthy subjects (green) with median values and interquartile ranges of the five identified genes. Panel b: Individual gene expression values in STEMI patients (red), and SCAD patients (orange) with median values and interquartile ranges of the five identified genes.

Figure 2

Receiver operating characteristic (ROC) curve for discriminating STEMI from HD and from SCAD. (a) The area under the ROC curve (AUC) of the capacity of the five identified genes to discriminate STEMI patients and HD (red line). AUC of 0.95 (95% confidence interval 0.62–1.00). (b) The area under the ROC curve (AUC) of the capacity of the five identified genes to discriminate STEMI and SCAD patients (red dotted line). AUC of 0.93 (95% confidence interval 0.60–1.00).