A Novel miRNA Screen Identifies miRNA-4454 as a Candidate Biomarker for Ventricular Fibrosis in Patients with Hypertrophic Cardiomyopathy

Abstract

(1) Background: Left ventricular hypertrophy, myocardial disarray and interstitial fibrosis are the hallmarks of hypertrophic cardiomyopathy (HCM). Access to the myocardium for diagnostic purposes is limited. Circulating biomolecules reflecting the myocardial disease processes could improve the early detection of HCM. Circulating miRNAs have been found to reflect disease processes in several cardiovascular diseases. (2) Methods: We quantified circulating miRNA molecules in the plasma of 24 HCM and 11 healthy controls using the Human v3 miRNA Expression Assay Kit Code set (Nanostring Tech., Seattle, WA, USA) and validated differentially expressed miRNAs using RT-PCR. (3) Results: In comparison to healthy controls, the levels of six miRNAs (miR-1, miR-3144, miR-4454, miR-495-3p, miR-499a-5p and miR-627-3p) were higher in the plasma of HCM patients than healthy individuals (p < 0.05). Of these, higher levels of miR-1, miR-495 and miR-4454 could be validated by real-time PCR. In addition, elevated miR-4454 levels were significantly correlated with cardiac fibrosis, detected by magnetic resonance imaging in HCM patients. (4) Conclusions: Circulating miR-1, miR-495-3p and miR-4454 levels are elevated in the plasma of HCM patients. To the best of our knowledge, this is the first report showing a correlation between miR-4454 levels and cardiac fibrosis in HCM. This suggests miR-4454 as a potential biomarker for fibrosis in these patients.

New Insights into the Functions of MicroRNAs in Cardiac Fibrosis: From Mechanisms to Therapeutic Strategies

“…They found that only miR-133a could be a biomarker independently associated with the decrease in thr carboxy-terminal propeptide of type-I collagen (PICP, (β-value = 6.43, 95% confidence interval (CI): 12.71 to −0.15), which would be correlated with collagen synthesis and myocardial fibrosis [ 111 , 112 ]. Recently, Thottakara et al reported that the plasma level of miR-4454 was significantly correlated with the extent of cardiac fibrosis detected by late gadolinium enhancement (LGE) on magnetic resonance imaging (MRI) (r = 0.56) and septal wall-thickness (r = 0.38) in patients with hypertrophic cardiomyopathy (HCM) [ 71 ].…”

Circulating miR-499a-5p Is a Potential Biomarker of MYH7—Associated Hypertrophic Cardiomyopathy

“…The literature regarding the association of circulating miR-499 with HCM is still limited and contradictory. The level of miR-499a-5p was higher in the plasma of HCM patients than of healthy controls [ 35 ]. In another study no significant differences were observed for miR-499-5p when analyzing 41 HCM patients and 41 age- and sex-matched healthy controls [ 16 ].…”

Differential Expression of microRNAs in Hypertrophied Myocardium and Their Relationship to Late Gadolinium Enhancement, Left Ventricular Hypertrophy and Remodeling in Hypertrophic Cardiomyopathy

“…MiR-499 was shown to regulate the cardiac β-MyHC/α-MyHC ratio, and β-MyHC expression was increased in human hearts of patients with ischemic cardiomyopathy and other heart diseases [ 23 , 24 , 25 , 26 ]. Circulating miR-499a-5p was proven as one of the dysregulated miRNAs in HCM, which expressed higher in HCM patients than in healthy controls, and carriers of P/LP variants in the MYH7 gene expressed higher levels than in controls [ 27 , 28 ]. In our study, we found that myocardial miR-499a-5p was also up-regulated, and higher expression of myocardial miR-499a-5p correlated with lower LVEF.…”