Abstract 19030: Negative Regulation of Atrial Natriuretic Peptide by MicroRNAs in Strained Human Cardiomyocytes
Introduction: Atrial natriuretic peptide (ANP) is a cardiac peptide hormone released by cardiomyocytes in response to myocardial strain and thought to have beneficial effects in heart failure (HF) patients. Recent studies have implicated three microRNAs (miRNAs) - miR-105, miR-155 and miR-425 - as posttranscriptional regulators of ANP, by binding and facilitating degradation of ANP mRNA. We wanted to study the effect of these miRNA on ANP expression in human cardiomyocytes subjected to strain, mimicking conditions for heart failure with elevated filling pressures.
Methods and Results: Cardiomyocytes derived from human induced pluripotent stem (iPS) cells were subjected to 10% uniaxial stretch for 48 hours. Subjecting iPS-derived cardiomyocytes to 60 cycles/minute resulted in a 3-fold increase in ANP expression and 1.2-fold increase in ANP secretion. Furthermore, miRNA-105 and miRNA-155 expression levels were significantly decreased (p<0.05). iPS-derived cardiomyocytes were then transfected with pre- and anti-miRNAs for each of the three miRNAs. pre-miRNA transfection resulted in lower expression of ANP for all three miRNAs (p<0.05). However, only transfection with anti-miRNA-155 resulted in a significant, 2.5-fold increase in NPPA expression. Furthermore, when cells were transfected with pre-miRNA-155 and then stretched for 48h, we observed that the stretch-dependent increase of NPPA gene expression could be diminished with pre-miRNA-155 (p<0.05).
Conclusions: We developed a model to study human ANP expression and observed increased ANP expression and secretion in response to strain. This increase was reduced when cells were treated with pre-miRNA-155. Additional work is needed to determine whether anti-miRNAs or target blockers can be used to enhance ANP secretion in response to strain, which could constitute a new therapeutic strategy for HF and hypertension.
Author Disclosures: S. Celik: None. C. Wu: None. E.S. Buys: None. D.B. Bloch: None. C. Newton-Cheh: None. J. Smith: None. O. Gidlöf: None.
- © 2016 by American Heart Association, Inc.