ANALYSIS OF GENE EXPRESSION IN THE DEVELOPMENT OF HEART FAILURE AFTER ACUTE MYOCARDIAL INFARCTION
Heart failure; acute myocardial infarction; gene expression; markers.
Heart failure (HF) is a progressive syndrome characterized by the heart's inability to pump enough blood to other tissues, and its main cause is acute myocardial infarction (AMI). Despite advances in identifying markers associated with left ventricular (LV) remodeling, the ideal marker for early and accurate detection of ischemic HF has not yet been found. Therefore, this study aims to evaluate the expression of 13 genes previously associated with AMI in patients with ischemic HF, comparing them with those who had no complications after AMI. In addition, this study sought to summarize the miRNAs most frequently cited in the literature as they are related to the development of ischemic HF and to verify their influence on the expression of the 13 genes. Patients who suffered previous AMI were classified into two groups: LV dysfunction [LV ejection fraction (LVEF) ≤ 40%, n = 14] and normal LV function (LVEF > 40%, n = 14). Expression of ALOX15, AREG, BCL2A1, BCL2L1, CA1, COX7B, ECHDC3, IL18R1, IRS2, KCNE1, MMP9, MYL4 and TREML4 were updated by RT-PCR. Only KCNE1 expression decreased in the LVEF ≤ 40% group (p = 0.007). A positive correlation was found between KCNE1 and ejection fraction (r = 0.557; p = 0.001). There was a 12.25-fold risk (95% CI: 1.33 - 113.06; p = 0.027) of LV dysfunction for patients with lower expression of KCNE1. KCNE1 expression showed high AUROC (AUROC: 0.811, 95% CI: 0.642-0.979, p = 0.007), indicating KCNE1 expression as a good predictor of cardiac outcomes. Literature analysis showed that miR-499, miR-1, miR-133a, and miR-208b are the miRNAs most associated with the development of ischemic HF. According to miRNet public database, miR-1 is already described as a regulator of KCNE1 expression. Thus, this study suggests that the expression of KCNE1, as well as its regulatory mechanisms such as miR-1, may be related to LVEF levels and, therefore, to the establishment of post-AMI HF.