Angiotensin II induces upregulation of AT1 receptors via the sequential activation of transcription factors NFkB, Elk‐1 and AP‐1 in Cath.a cells

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It has been clearly established that increased circulating Angiotensin II (Ang II) with concurrent upregulation of brain and peripheral Angiotensin 1‐receptors (AT1R) are important mediators in the pathophysiology of heart failure. In this study we aim to determine the role of sequential activation of transcription factors NFκB, AP‐1 and Elk‐1 in AT1R upregulation. We used Cath.a cells as our neuronal cell model which was treated with Ang II (100nM) over a time course. Western blotting was done for protein expression. Following Ang II activation, there was a temporal increase of the p65 subunit of NFkB. There was a concomitant decrease of IκB and increased IκK expression and AT1R expression. The activation of NFκB was blocked by using the inhibitor Parthenolide leading to a decrease in AT1R expression. The expression of Elk‐1 was upregulated following Ang II activation and was decreased following NFκB inhibition. Gene silencing using p65‐siRNA had similar effects as Parthenolide. The data are presented in the table. Our results suggest a combined role of NFκB, Elk‐1 and AP‐1 in the upregulation AT‐1R in Cath.a cells.Table showing fold change in protein expression compared to control. *p<0.01 vs. control.