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. Author manuscript; available in PMC: 2017 Apr 15.
Published in final edited form as: Circ Res. 2016 Apr 15;118(8):1313–1326. doi: 10.1161/CIRCRESAHA.116.307708

Figure 2. Transcriptional, post-transcriptional, and post-translational regulation of ACE2.

Figure 2

ACE2 expression is transcriptionally regulated by energy stress and activation of AMPK via SIRT1, which binds to the promoter region and facilitates ACE2 mRNA expression. Similarly, apelin binds to the promoter region of ACE2 and enhances its expression. ACE2 mRNA is subject to post-transcriptional regulation by miR-421, which regulates protein expression. Ang II, the main effector peptide of the RAS, is produced by ACE and chymase in the heart and other tissues. ACE2, a monocarboxypeptidase, degrades Ang II into a heptapetide, Ang 1–7. Ang II, via its action on AT1R, promotes NOX2-dependent ROS formation. This leads to phosphorylation and activation of p38-MAPK and ultimately results in TACE phosphorylation (Thr735) and activation. Activated TACE proteolytically cleaves ACE2 and releases the active ACE2 ectodomain.