Abstract
Sustained cardiac hypertrophy (CH) contributes to many heart diseases. Long noncoding RNAs (lncRNAs) collectively play critical roles in cardiovascular diseases (CVDs). However, the roles of lncRNA H19 in CH are still unclear. A CH model was constructed utilizing isoproterenol (ISO). We demonstrated H19 could participate in regulating ISO-induced CH development both in vivo and in vitro. The online databases DIANA and TargetScan were used to predict the targets of H19 and MicroRNA-145-3p (miR-145-3p), respectively. Luciferase reporter assay was used to verify the downstream targets. The results showed that H19 was decreased under ISO stimulation. The H19 overexpression resulted in significant decrease in mouse heart size and weight, left ventricular systolic dysfunction, left ventricular posterior wall thickness and cardiac hypertrophic growth, while promoted the increase of left ventricular ejection fraction and left ventricle fraction shortening. H19 also inhibited protein expression levels of CH markers, such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and MYH7. Luciferase assays results showed that miR-145-3p was a target of H19 and SMAD4 was a target of miR-145-3p. We found that H19 regulated SMAD4 by sponging miR-145-3p. Knockout of miR-145-3p or overexpression of SMAD4 facilitated H19-induced decreases in ANP, BNP, and MYH7. Collectively, our findings have indicated that the H19/miR-145-3p/SMAD4 axis should be a negative regulator involved in CH progression.