Nuclear Receptor RORα Functions as a Transcriptional Activator of Alpha-1A-Adrenergic Receptor

Upregulation of the A subtype of alpha-1 adrenergic receptors (alpha-1A-ARs) is linked to cardioprotection during heart failure. Similarly, the transcription factor retinoid-related orphan receptor alpha (RORα) is upregulated to provide cardioprotection and has also been shown to contribute to adaptive changes in cardiomyocyte biology during heart failure. Though both alpha-1A-ARs and RORα contribute to cardioprotection and are both present in cardiomyocytes, a link between the two has not yet been found. In this paper, we show that RORα acts as a transcription factor regulating α1a levels in cardiomyocytes. We initially found through microarray analysis of heart tissue that α1A-ARs are expressed at significantly lower levels in the hearts of RORα knockout mice. Further analysis through quantitative reverse transcriptase polymerase chain reaction (qPCR) showed a decrease in alpha-1A-AR expression level in global and cardiomyocyte-specific RORα knockout mice. These results suggest that RORα might act as a transcriptional regulator of α1A, potentially linking the cardioprotective effects of α1a and RORα. Establishing a link between two important cardioprotective mechanisms may contribute to a better understanding of positive clinical outcomes in human heart failure, and may potentially open a new route for therapeutics to treat heart failure.Bachelor of Scienc