Background: Cardaic muscle contractile and metabolic phenotype are subject to pathophysiological regulation. Hypertension and progression to heart failure results in an increase of slow/beta myosin heavy chain (β-MHC) that is mediated by the transcriptional activation of the MYH7 gene. We previously discovered several long non-coding (lnc) RNAs by RACE PCR and sequencing that are transcribed from the antisense (AS) strand of the MYH7 gene, thus named MYH7-AS. These lncRNAs appear to have distinct transcription start sites downstream from MHRT, another MYH7-associated lncRNA previously shown to protect the heart from hypertrophy and failure. Variants of MYH7-AS contain an exon that partially overlaps and is complementary to the microRNA (miR) 208b, which is encoded in a MYH7 intron.

Objective: test the hypothesis that MYH7-AS levels are decreased by aortic banding, in association with β-MHC upregulation, thereby implicating its role in regulating cardiac MYH7 that occurs as a compensatory response to pressure and volume overload.

Methods: We induced cardiac hypertrophy in rats with the pressure overload surgical procedure of thoracic aortic banding of the ascending aorta (AAB) for 16 days and compared this to a sham surgery group (N=6). RNA expression was examined by real-time PCR.

Results: Cardiac mass (heart weight/body weight ratio) was increased by 29% in response to AAB. M-mode echocardiographic parameters of cardiac left ventricle at the time of sacrifice such as interventricular septal thickness (+24%) and left ventricular free wall thickness (+32%) were similarly increased. Other mRNA markers of cardiac hypertrophy (ANP, BNP, α-MHC) were also responsive to AAB. These data indicate that the AAB effectively induced cardiac hypertrophy at the acute stage of cardiac failure. MYH7 mRNA was significantly increased in left ventricle after AAB as compared to sham (2.1-fold), and there was a corresponding 4.2-fold less expression of MYH7-AS with AAB.

Conclusions: Further research will be needed to determine if MYH7-AS could be utilized for exogenous delivery as a therapeutic approach to inhibit β-MHC upregulation in the hypertrophic heart and thereby preserve cardiac function and protect the heart from failure.

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