Key result
miR-19a/b-3p directly targets PDE5A and prevents the progression of cardiac hypertrophy and remodeling in response to angiotensin II infusion in mouse models.
Why the study?
Does miR-19a/b-3p overexpression prevent cardiac hypertrophy and remodeling in mouse models?
Does miR-19a/b-3p overexpression prevent cardiac hypertrophy and remodeling in mouse models?
miR-19a/b-3p protects against angiotensin II-induced cardiac hypertrophy and remodeling by directly targeting PDE5A, suggesting a potential therapeutic target for heart failure.
These animal findings are hypothesis-generating for miR-19 regulation of PDE5A; human studies needed before clinical consideration.
AIM: PDE5A is a leading factor contributing to cGMP signaling and cardiac hypertrophy. However, microRNA-mediated posttranscriptional regulation of PDE5A has not been reported. The aim of this study is to screen the microRNAs that are able to regulate PDE5A and explore the function of the microRNAs in cardiac hypertrophy and remodeling. METHODS AND RESULTS: Although miR-19a/b-3p (microRNA-19a-3p and microRNA-19b-3p) have been reported to be differentially expressed during cardiac hypertrophy, the direct targets and the functions of this microRNA family for regulation of cardiac hypertrophy have not yet been investigated. The present study identified some direct targets and the underlying functions of miR-19a/b-3p by using bioinformatics tools and gene manipulations within mouse neonatal cardiomyocytes. Transfection of miR-19a/b-3p down-regulated endogenous expressions of PDE5A at both mRNA and protein levels with real-time PCR and western blot. Luciferase reporter assays showed that PDE5A was a direct target of miR-19a/b-3p. In mouse models of cardiac hypertrophy, we found that miR-19a/b-3p was expressed in cardiomyocytes and that its expression was reduced in pressure overload-induced hypertrophic hearts. miR-19a/b-3p transgenic mice prevented the progress of cardiac hypertrophy and cardiac remodeling in response to angiotensin II infusion with echocardiographic assessment and pressure-volume relation analysis. CONCLUSION: Our study elucidates that PDE5A is a novel direct target of miR-19a/b-3p, and demonstrates that antihypertrophic roles of the miR-19a/b-3p family in Ang II-induced hypertrophy and cardiac remodeling, suggests that endogenous miR-19a/b-3p might have clinical potential to suppress cardiac hypertrophy and heart failure.
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Liu et al. (2018) studied Cardiac hypertrophy. miR-19a/b-3p was evaluated on PDE5A expression and cardiac hypertrophy/remodeling. miR-19a/b-3p directly targets PDE5A and prevents the progression of cardiac hypertrophy and remodeling in response to angiotensin II infusion in mouse models.
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