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. 2019 May 17;9(5):193.
doi: 10.3390/biom9050193.

Clinical Value of Circulating Microribonucleic Acids miR-1 and miR-21 in Evaluating the Diagnosis of Acute Heart Failure in Asymptomatic Type 2 Diabetic Patients

Mutaa Abdalmutaleb Al-Hayali  1   2 , Volkan Sozer  3 , Sinem Durmus  4 , Fusun Erdenen  5 , Esma Altunoglu  6 , Remise Gelisgen  7 , Pınar Atukeren  8 , Palmet Gun Atak  9 , Hafize Uzun  10
Affiliations

Clinical Value of Circulating Microribonucleic Acids miR-1 and miR-21 in Evaluating the Diagnosis of Acute Heart Failure in Asymptomatic Type 2 Diabetic Patients

Mutaa Abdalmutaleb Al-Hayali et al. Biomolecules. .

Abstract

To investigate whether the circulating miR-1 (microRNA-1) and miR-21 expression might be used in the diagnosis of heart failure (HF) and silent coronary artery disease (SCAD) in asymptomatic type 2 diabetes mellitus (T2DM) patients and to explore the relationship of these miRs with N-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3. One hundred thirty-five consecutive patients with T2DM and 45 matched control subjects were enrolled in the study. This study consisted of the following four groups: control group (mean age: 60.23 ± 6.27 years, female/male (F/M): 23/22); diabetic group (DM) (mean age: 61.50 ± 5.08, F/M: 23/22); DM + SCAD group (mean age: 61.61 ± 6.02, F/M: 20/25); and DM + acute HF group (mean age: 62.07 ± 5.26 years, F/M: 20/25). miR-1 was downregulated in the DM, CAD + DM and HF + DM groups by 0.54, 0.54, and 0.12 fold as compared with controls, respectively. The miR-1 levels were significantly lower in HF + DM than DM with 0.22 fold changes (p < 0.001); and in patients with CAD + DM group with 0.22 fold changes (p < 0.001). Similarly, miR-21 was overexpressed in patients with DM, CAD + DM, and HF + DM with 1.30, 1.79 and 2.21 fold changes as compared with controls, respectively. An interesting finding is that the miR-21 expression was significantly higher in the HF + DM group as compared with the CAD + DM group; miR-1 was negatively correlated with NT-proBNP (r = -0.891, p < 0.001) and galectin-3 (r = -0.886, p < 0.001) in the HF + DM group; and miR-21 showed a strongly positive correlation with (r = 0.734, p < 0.001) and galectin-3 (r = 0.764. p < 0.001) in the HF + DM group. These results suggest that the circulating decreased miR-1 and increased miR-21 expression are associated with NT-proBNP and galectin-3 levels in acute HF + DM. Especially the miR-21 expression might be useful in predicting the onset of acute HF in asymptomatic T2DM patients. The miR-21 expression is more valuable than the miR-1 expression in predicting cardiovascular events of acute HF and the combined analysis of miR-21 expression, galectin-3, and NT-proBNP can increase the predictive value of miR-21 expression.

Keywords: NT-proBNP; acute heart failure; asymptomatic type 2 diabetes mellitus; galectin-3; miRNA-1; miRNA-21; silent coronary artery disease.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Relative expression levels of miR-1. The miR-1 levels were significantly lower in patients from the DM, CAD + DM and HF + DM groups than in the control groups, with 0.54-, 0.54- and 0.12-fold changes, respectively. The miR-1 levels were significantly lower in patients from the HF + DM group than in patients with DM with 0.22-fold changes; and in patients from the CAD + DM group with 0.22-fold changes. Data are presented as fold-change derived from mean 2−ΔΔCT method. *** p < 0.001.
Figure 2
Figure 2
Relative expression levels of miR-21. The miR-21 levels were significantly higher in patients from the CAD + DM and HF + DM groups than the control groups, with 1.79-, and 2.21-fold changes, respectively. The miR-21 levels were significantly higher in patients from the HF + DM group than in patients with DM with 1.70-fold changes, and in patients from the CAD + DM group with 1.24-fold changes, and in patients from the CAD + DM group than in patients with DM with 1.37-fold changes. Data are presented as fold-change derived from mean 2−ΔΔCT method. ** p < 0.01 *** p < 0.001.
Figure 3
Figure 3
The miR-1 correlations with NT-proBNP and galectin-3 in the DM, CAD + DM and HF + DM groups. Data are presented as fold-change derived from mean 2−ΔΔCT method. Rs: Spearman’s rank correlation coefficients (r) (A) miR-1 vs. NT-proBNP in DM group; (B) miR-1 vs. galectin-3 in DM group; (C) miR-1 vs. NT-proBNP in CAD + DM group; (D) miR-1 vs. galectin-3 in CAD + DM group; (E) miR-1 vs NT-proBNP in HF + DM group; (F) miR-1 vs galectin-3 in HF + DM group.
Figure 3
Figure 3
The miR-1 correlations with NT-proBNP and galectin-3 in the DM, CAD + DM and HF + DM groups. Data are presented as fold-change derived from mean 2−ΔΔCT method. Rs: Spearman’s rank correlation coefficients (r) (A) miR-1 vs. NT-proBNP in DM group; (B) miR-1 vs. galectin-3 in DM group; (C) miR-1 vs. NT-proBNP in CAD + DM group; (D) miR-1 vs. galectin-3 in CAD + DM group; (E) miR-1 vs NT-proBNP in HF + DM group; (F) miR-1 vs galectin-3 in HF + DM group.
Figure 4
Figure 4
The miR-21 correlations with NT-proBNP and galectin-3 in the DM, CAD + DM and HF + DM groups. Data are presented as fold-change derived from mean 2−ΔΔCT method. Rs: Spearman’s rank correlation coefficients (r). (A) miR-21 vs. NT-proBNP in DM group; (B) miR-21 vs. galectin-3 in DM group; (C) miR-21 vs. NT-proBNP in CAD + DM group; (D) miR-21 vs galectin-3 in CAD + DM group; (E) miR-21 vs. NT-proBNP in HF + DM group; (F) miR-21 vs galectin-3 in HF + DM group.
Figure 4
Figure 4
The miR-21 correlations with NT-proBNP and galectin-3 in the DM, CAD + DM and HF + DM groups. Data are presented as fold-change derived from mean 2−ΔΔCT method. Rs: Spearman’s rank correlation coefficients (r). (A) miR-21 vs. NT-proBNP in DM group; (B) miR-21 vs. galectin-3 in DM group; (C) miR-21 vs. NT-proBNP in CAD + DM group; (D) miR-21 vs galectin-3 in CAD + DM group; (E) miR-21 vs. NT-proBNP in HF + DM group; (F) miR-21 vs galectin-3 in HF + DM group.
Figure 5
Figure 5
The ROC analysis of laboratory findings for different groups: (A) Control vs. DM groups, (B) Control vs. CAD + DM groups, (C) Control vs. HF + DM groups, (D) DM vs. CAD + DM groups, (E) DM vs. HF + DM groups, and (F) CAD + DM vs. HF + DM vs. CAD + DM groups.
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