Molecular effects of Ang II‐mediated differential ACE2 expression in cultured rat astrocytes (1140.2)

Abstract

Objective: Angiotensin (Ang) II effects on Angiotensin Converting Enzyme 2 (ACE2) in spontaneous hypertensive rats (SHR) was determined. Background: ACE2 is a negative regulator of the renin angiotensin system catalyzing the conversion of Ang II to Ang‐(1‐7), a peptide that counteracts Ang II effects. Methods: Brainstem (BS) and cerebellum (CB) astrocytes isolated from SHR and Wistar rats were used in this study. Cells were treated with 100nM Ang II at various times and ACE2 protein, and mRNA levels measured using Western blot and qPCR techniques, respectively. Results: Ang II showed a differential pattern to affect ACE2 protein levels in Wistar and SHR astrocytes. Most treatment groups showed ACE2 protein levels significantly reduced compared to basal ACE2 protein. There was a significant difference in Ang II‐mediated ACE2 protein levels in Wistar versus SHR astrocytes. Similarly, Ang II treatment had a differential pattern to modulate mRNA levels of ACE2 in these cells. In SHR CB astrocytes, the pattern of Ang II effects on ACE2 mRNA was significantly different compared to Wistar astrocytes. However, the effects of Ang II were mostly similar in BS Wistar and SHR cells. Conclusion: These findings suggest that the hypertensive state in the SHR may significantly affect Ang II’s ability to influence ACE2 mRNA expression but this effect did not translate into differences in ACE2 protein expression.Grant Funding Source: Supported by Nova Southeastern University Chancellor's Faculty Research & Development Grant # 335872