Different levels of microRNA expression (miR-30c-5p, miR-221-3p and miR-375-3p) in heart failure patients with preserved and reduced ejection fraction

A comparative analysis of the gene expression of microRNAs miR-148b-3p, miR- 30c-5p, miR-221-3p, miR-328-3p, miR-146a-5p, miR-375-3p, miR-22-3p, miR-15b-3p, miR-148a-3p, miR-590-5p in peripheral blood mononuclear cells (PBMC) and epicardial adipose tissue of coronary heart disease (СHD) patients with and without HF (Non-HF) was carried out. Among СHD patients with HF, the groups with mildly reduced/reduced and preserved ejection fraction (HFmr/rEF and HFpEF, respectively) were compared. Our study revealed a significant increase in the expression of miR-30c-5p, miR-221-3p and miR-375-3p mi croRNAs in PBMCs of patients with HFmr/rEF and HFpEF compared with the group of СHD patients without HF. Accordingly, the relative level of miR-30c-5p expression in PBMC of HFF/EFV patients was significantly higher by 1.99 times in comparison with patients without HF (P<0.0001). The expression of this microRNA in PBMC of HFpEF patients relative to patients without HF is significantly higher by 2.94-fold (P<0.0001). The expression level of miR-221-3p in PBMC of HFpEF patients was increased 4.04-fold relative to patients without HF (P<0.0001). A 2.63-fold increase in miR-221-3p expression was detected in PBMC of HFmr/rEF patients (P<0.0001). The expression of miR-375-3p in PBMCs of HFmr/rEF and HFpEF patients compared with Non-HF patients was significantly higher by 2.09- and 1.77 fold (P<0.0001). For all other investigated microRNAs, no significant expression changes were detected in PBMC. Similarly, we did not detect significant expression changes for any of the investigated microRNA genes in the epicardial adipose tissue of CHD patients. Thus, the obtained data can be used to determine the role of the investigated microRNAs in the pathogenesis of HF in СHD patients. 

1. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Fail ure Association (HFA) of the ESC. Eur J Heart Fail. 2022; 24(1): 4-131. DOI: 10.1002/ejhf.2333.

2. Banerjee A, Mendis S. Heart fail ure: the need for global health perspective. Curr Cardiol Rev. 2013; 9(2): 97-8. DOI: 10.2174/1573403x11309020001.

3. Böyum A. Separation of leukocytes from blood and bone marrow. Introduction. Scand J Clin Lab Invest Suppl. 1968; 97: 7.

4. Parvan R, et al. Diagnostic performance of microRNAs in the detection of heart failure with reduced or preserved ejection fraction: a sys tematic review and meta-analysis. Eur J Heart Fail. 2022; 24(12): 2212-2225. DOI: 10.1002/ ejhf.2700. 5. Zhang L, et al. Diagnostic value of circu lating microRNA-19b in heart failure. Eur J Clin Invest. 2020; 50(11): e13308. DOI: 10.1111/eci.13308.

5. Groenewegen A, et al. Epidemiology of heart failure. Eur J Heart Fail. 2020; 22(8): 1342 1356. DOI: 10.1002/ejhf.1858.

6. Hahn MW, Wray GA. The g-value paradox. Evol Dev. 2002; 4(2): 73-5. DOI: 10.1046/j.1525 142x.2002.01069.x. 8. Savarese G, et al. Heart failure with mid range or mildly reduced ejection fraction. Nat Rev Cardiol. 2022; 19(2): 100-116. DOI: 10.1038/s41569-021-00605-5.

7. Jin Z. Q. MicroRNA targets and biomarker validation for diabetes-associated cardiac fibro sis. Pharmacol Res. 2021; 174:105941. DOI: 10.1016/j.phrs.2021.105941.

8. Liu G, Mattick JS, Taft RJ. A meta-analysis of the genomic and transcriptomic composition of complex life. Cell Cycle. 2013; 12(13): 2061-72. DOI: 10.4161/cc.25134.

9. Livak KJ, Schmittgen TD. Analysis of rel ative gene expression data using real-time quan titative PCR and the 2(-Delta Delta C(T)) Meth od. Methods. 2001; 25(4): 402-8. DOI: 10.1006/meth.2001.1262.

10. Ning BB, et al. Luteolin-7-diglucuronide at tenuates isoproterenol-induced myocardial injury and fibrosis in mice. Acta Pharmacol Sin. 2017; 38(3): 331-341. DOI: 10.1038/aps.2016.142.

11. Feng H, et al. MicroRNA-375-3p inhibitor suppresses angiotensin II-induced cardiomyocyte hypertrophy by promoting lactate dehydroge nase B expression. J Cell Physiol. 2019; 234(8): 14198-14209. DOI: 10.1002/jcp.28116.

12. Chen J, et al. Rno-microRNA-30c-5p pro motes myocardial ischemia reperfusion injury in rats through activating NF-κB pathway and target ing SIRT1. BMC Cardiovasc Disord. 2020; 20(1): 240. DOI: 10.1186/s12872-020-01520-2.

13. Garikipati VNS, et al. Therapeutic inhi bition of miR-375 attenuates post-myocardial infarction inflammatory response and left ventric ular dysfunction via PDK-1-AKT signalling axis. Cardiovasc Res. 113(8): 938-949. DOI: 10.1093/cvr/cvx052.

14. Ruddick-Collins LC, et al. Timing of dai ly calorie loading affects appetite and hunger responses without changes in energy metabo lism in healthy subjects with obesity. Cell Metab. 2022; 34(10): 1472-1485.e6. DOI: 10.1016/j.cmet.2022.08.001