Abstract 13358: LincRNAs Regulated by Pressure-overload Induce Hypertrophy in Neonatal Mouse Ventricular Cardiomyocytes
Rationale: Recent genome-wide approaches have revealed that long intergenic non-coding RNAs (lincRNAs) are transcribed from many intervening regions of protein coding genes. Several reports indicate that lincRNAs have pivotal role in physiological and pathological conditions such as cancer and cell reprogramming. However, it is still unclear whether lincRNAs are involved in cardiac hypertrophy or cardiac remodeling resulting in heart failure.
Methods and Results: To identify the up-regulated intervening regions of protein coding genes during cardiac remodeling, we extracted the total RNAs from the heart after transverse aortic constriction (TAC) in mice, and carried out microarray analysis. We identified 10 transcribed regions, and transcripts derived from these regions were named lincRNA-Hypertrophy (linc-hypertrophy). The levels of three lincRNA-Hypertrophys (linc-hypertrophy3, -hypertrophy5, and -hypertrophy7) were validated based on qRT-PCR (n = 4-6, p<0.05). The expression levels of linc-hypertrophy3, -hypertrophy5, and -hypertrophy7 were up-regulated in neonatal mouse ventricular cardiomyocytes stimulated with angiotensin II and phenylephrine in a dose dependent manner (n = 4-7, p<0.05). Of these 3 linc-hypertrophy, we unveiled the full length transcripts of 2 lincRNAs (linc-hypertrophy5 and -hypertrophy7) using 5’ and 3’ rapid amplification of cDNA ends. Furthermore, overexpression of linc-hypertrophy5 and linc-hypertrophy7 significantly increased mRNA levels of hypertrophy associated genes, including ANF (linc-hypertrophy5: n = 3, p<0.01; linc-hypertrophy7: n = 3, p<0.001) and BNP (linc-hypertrophy5: n = 3, p<0.01; linc-hypertrophy7: n =3, p<0.001), and cell surface area of neonatal mouse ventricular cardiomyocytes (linc-hypertrophy5: p<0.05; linc-hypertrophy7: p<0.001).
Conclusions: These results suggest that transcription of numerous lincRNAs were up-regulated during cardiac remodeling, and some lincRNAs were involved in neonatal mouse cardiomyocyte hypertrophy. Since ectopic expressions of lincRNA-Hypertrophy induced cardiomyocyte hypertrophy, lincRNAs may be key players in cardiac hypertrophy.
- © 2013 by American Heart Association, Inc.