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.
Highlights
Heart failure (HF) is one of the leading causes of hospital admission and mortality worldwide [1]
Echocardiographic left ventricular internal end diastolic dimension (LVIDd) and left ventricular internal end systolic dimension (LVIDs) values were significantly increased from 4 weeks post-Myocardial infarction (MI) to 8 weeks post-MI and mildly increased from 8 weeks post-MI to 12 weeks post-MI (Figure 1(a))
We found that the cardiomyocyte size in an area distant from the site of infarction was larger in the 4-week post-MI and 8-week post-MI groups than in the corresponding sham groups, and this cardiomyocyte hypertrophy was attenuated at 12 weeks post-MI (Figure 1(b))
Summary
Heart failure (HF) is one of the leading causes of hospital admission and mortality worldwide [1]. Myocardial infarction (MI) is a common predisposing cause of HF [1]. Following MI, progressive left ventricular remodeling occurs in the noninfarcted myocardium and plays a central role in the pathophysiology of HF [2, 3]. Left ventricular remodeling is characterized by left ventricular dilatation, hypertrophy, distortion of contour, activation of interstitial fibrosis, and deterioration in cardiac dysfunction [2,3,4]. In clinical practice, circulating biomarkers such as natriuretic peptides associated with cardiac overload facilitate the clinical management of HF [1]. There is a need to find reliable circulating biomarkers for tracking the process of left ventricular remodeling to help clinicians recognize high-risk patients for more aggressive prevention as early as possible
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
