Differential expression of circulating miRNAs as a novel tool to assess BAG3-associated familial dilated cardiomyopathy.
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2019
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Bioscience Reports
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Abstract
A new familial dilated cardiomyopathy (FDCM) was found related to mutations in BAG3
gene. MicroRNAs (miRNAs) represent new targets of FDCM, although no studies have assessed
clinical association between Bcl2-associated athanogene 3 (BAG3)-related DCM
and miRNAs. Here, we studied whether a clinical association between BAG3-related FDCM
and circulating miRNAs may have diagnostic and prognostic value in a small cohort of familial
related individuals carrying a BAG3 mutation (BAG3+) and/or diagnosed of dilated cardiomyopathy
(DCM) (DCM+). The analysis of 1759 circulating miRNAs showed significant
differences between BAG3+ and BAG3- individuals for miRNAs mir-3191-3p, 6769b-3p,
1249-ep, 154-5p, 6855-5p, and 182-5p, while comparisons between BAG3+/DCM+ versus
BAG3+/DCM- were restricted to miRNAs mir-154-5p, 6885-5p, and 182-5p, showing significant
correlation with systolic and diastolic blood pressure, A wave, left atrium length, and
left atrium area. Additionally, when stratified by gender and age, miRNAs were statistically
correlated with critical parameters, including left ventricle ejection fraction (LVEF) and ventricular
diameter, in women and young men. Likewise, 56% of BAG3+/DCM+, significantly
co-expressed mir-154-5p and mir-182-5p, and a slight 4% did not express such combination,
suggesting that co-expression of mir-154-5p and mir-182-5p may potentially show
diagnostic value. Further studies will require long-term follow-up, and validation in larger
populations.