Circulating MicroRNAs as Novel Potential Biomarkers for Left Ventricular Remodeling in Postinfarction Heart Failure

Abstract

Circulating microRNAs (miRNAs) have been proposed as potential biomarkers for left ventricular remodeling in postinfarction heart failure (HF). However, the diagnostic reproducibility of the use of circulating miRNAs may be affected by the temporal expression of miRNAs following myocardial infarction (MI). In the current study, using a MI-induced HF rat cohort (4-, 8-, and 12-week post-MI groups), we investigated the temporal expression of plasma miRNAs during the development of left ventricular remodeling. The plasma miRNA expression profile was obtained using miRNA sequencing. The expression of candidate miRNAs in plasma and tissues was examined with real-time PCR. Target genes of candidate miRNAs were predicted using a parallel miRNA-messenger RNA expression profiling approach. The value of plasma miRNAs as biomarkers for left ventricular remodeling was evaluated in patients with postinfarction HF (n = 32) and control patients with stable angina and without significant coronary lesions and HF (n = 16) with real-time PCR. Although the expression levels of miR-20a-5p, miR-340-5p, and let-7i-5p were temporally regulated in plasma, myocardium, and peripheral blood mononuclear cells, the expression levels of plasma miRNAs, especially miR-20a-5p, were associated with the development of left ventricular remodeling in the postinfarction HF rat cohort. The target genes of these 3 miRNAs were associated with the mechanistic target of rapamycin, nuclear factor-κB, tumour necrosis factor, apoptosis, and p53 signaling pathways. Additionally, the plasma levels of miR-20a-5p, miR-340-5p, and let-7i-5p were significantly increased in patients with postinfarction HF. However, only the expression levels of miR-20a-5p presented significant positive correlations with left ventricular internal end diastolic dimension and left ventricular end diastolic volume. In conclusion, the expression levels of plasma miR-20a-5p were significantly associated with the degree of left ventricular dilatation, and plasma miR-20a-5p may be a potential biomarker for postinfarction left ventricular remodeling.

Effect of miR-195-5p on cardiomyocyte apoptosis in rats with heart failure by regulating TGF-β1/Smad3 signaling pathway

“…Recent studies have found that cardiomyocyte apoptosis may be a crucial part of HF pathogenesis [5]. Previous studies [6] have shown that cardiomyocyte apoptosis is very obvious in patients with HF. Therefore, it is quite significant to explore the mechanism of cardiomyocyte apoptosis in HF patients and how to prevent it for HF treatment.…”

“…As a non-coding short-chain RNA, miRNA can play a biological regulatory role by combining with target genes. Recently, miRNA has been found to be effective in all kinds of diseases, including cardiovascular diseases [6]. miR-195-5p has been proved to be down-regulated in coronary artery blood flow disorders in the past [7], which suggests that miR-195-5p may be effective in the development and progression of cardiovascular diseases.…”

CircUSP36 knockdown alleviates oxidized low‑density lipoprotein‑induced cell injury and inflammatory responses in human umbilical vein endothelial cells via the miR‑20a‑5p/ROCK2 axis

“…Accumulating evidence has suggested that miRNAs can be used as diagnostic and therapeutic markers for AS and that they regulate the pathologies of vascular diseases ( 15 , 16 ). Previous studies have demonstrated that miR-20a-5p is involved in the development of cardiovascular diseases ( 17 , 18 ). Research into the role of miR-20a-5p in ox-LDL-induced HUVECs is not limited.…”

Integrated Analysis of circRNA-miRNA-mRNA ceRNA Network in Cardiac Hypertrophy

“…The targeting interaction relationship between miR-27b-3p and Tgfbr3 appeared in our prediction results, which further indicated that the miR-27b-3p/Tgfbr3 axis may play a significant role in myocardial hypertrophy. The expression level of plasma miR-20a-5p was proportional to the degree of left ventricular remodeling and dilation after myocardial infarction ( Gao et al, 2019 ). The level of miR-342-3p in circulating miRNAs in heart failure model mice was significantly reduced ( Kaneko et al, 2017 ).…”