MiRNA-21a, miRNA-145, and miRNA-221 Expression and Their Correlations with WNT Proteins in Patients with Obstructive and Non-Obstructive Coronary Artery Disease.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Atherosclerosis* ; Coronary Artery Disease*/metabolism ; MicroRNAs*/genetics ; MicroRNAs*/metabolism ; Wnt Signaling Pathway*/genetics; Female ; Humans ; Male ; Cross-Sectional Studies ; Sirtuin 1/metabolism ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; Wnt4 Protein/genetics

MicroRNAs and the WNT signaling cascade regulate the pathogenetic mechanisms of atherosclerotic coronary artery disease (CAD) development.
Objective: To evaluate the expression of microRNAs (miR-21a, miR-145, and miR-221) and the role of the WNT signaling cascade (WNT1, WNT3a, WNT4, and WNT5a) in obstructive CAD and ischemia with no obstructive coronary arteries (INOCA).
Method: The cross-sectional observational study comprised 94 subjects. The expression of miR-21a, miR-145, miR-221 (RT-PCR) and the protein levels of WNT1, WNT3a, WNT4, WNT5a, LRP6, and SIRT1 (ELISA) were estimated in the plasma of 20 patients with INOCA (66.5 [62.8; 71.2] years; 25% men), 44 patients with obstructive CAD (64.0 [56.5; 71,0] years; 63.6% men), and 30 healthy volunteers without risk factors for cardiovascular diseases (CVD).
Results: Higher levels of WNT1 (0.189 [0.184; 0.193] ng/mL vs. 0.15 [0.15-0.16] ng/mL, p < 0.001) and WNT3a (0.227 [0.181; 0.252] vs. 0.115 [0.07; 0.16] p < 0.001) were found in plasma samples from patients with obstructive CAD, whereas the INOCA group was characterized by higher concentrations of WNT4 (0.345 [0.278; 0.492] ng/mL vs. 0.203 [0.112; 0.378] ng/mL, p = 0.025) and WNT5a (0.17 [0.16; 0.17] ng/mL vs. 0.01 [0.007; 0.018] ng/mL, p < 0.001). MiR-221 expression level was higher in all CAD groups compared to the control group ( p < 0.001), whereas miR-21a was more highly expressed in the control group than in the obstructive ( p = 0.012) and INOCA ( p = 0.003) groups. Correlation analysis revealed associations of miR-21a expression with WNT1 (r = -0.32; p = 0.028) and SIRT1 (r = 0.399; p = 0.005) protein levels in all CAD groups. A positive correlation between miR-145 expression and the WNT4 protein level was observed in patients with obstructive CAD (r = 0.436; p = 0.016). Based on multivariate regression analysis, a mathematical model was constructed that predicts the type of coronary lesion. WNT3a and LRP6 were the independent predictors of INOCA ( p < 0.001 and p = 0.002, respectively).
Conclusions: Activation of the canonical cascade of WNT-β-catenin prevailed in patients with obstructive CAD, whereas in the INOCA and control groups, the activity of the non-canonical pathway was higher. It can be assumed that miR-21a has a negative effect on the formation of atherosclerotic CAD. Alternatively, miR-145 could be involved in the development of coronary artery obstruction, presumably through the regulation of the WNT4 protein. A mathematical model with WNT3a and LRP6 as predictors allows for the prediction of the type of coronary artery lesion.

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22-15-00424 Russian Science Foundation

Keywords: SIRT1; WNT cascade proteins (WNT1, WNT3a, WNT4, WNT5a, LRP6); cardiovascular diseases; coronary artery disease; ischemia with no obstructive coronary arteries; microRNA (miR-21a, miR-145, miR-221)

0 (MicroRNAs)
0 (MIRN145 microRNA, human)
0 (MIRN221 microRNA, human)
EC 3.5.1.- (Sirtuin 1)
0 (Wnt Proteins)
0 (Wnt4 Protein)
0 (MIRN21 microRNA, human)

Date Created: 20231223 Date Completed: 20240111 Latest Revision: 20240111

20240111

PMC10744268

10.3390/ijms242417613

38139440