Análise da expressão gênica na disfunção ventricular após o infarto agudo do miocárdio
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 earl...
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| Formato: | doctoralThesis |
| Idioma: | pt_BR |
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Universidade Federal do Rio Grande do Norte
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| Endereço do item: | https://repositorio.ufrn.br/handle/123456789/44619 |
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| Resumo: | 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 LV dysfunction after AMI, 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 RTPCR. 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 risk of development of post-AMI HF. |
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