Nedd4-2 upregulation is associated with ACE2 ubiquitination in hypertension.

While ACE2 conversion of Ang-II to Ang-(1-7) is supposed to limit the overactivity of the renin-angiotensin system (RAS), the enzyme is downregulated during the development of hypertension. As antihypertensive RAS blockers on the market only provide limited control of BP among hypertensive patients, understanding the mechanisms responsible for this blunted compensation provides new possible targets for the treatment of hypertension. In this study we show that Nedd4-2 upregulation is associated with ACE2 ubiquitination while prevention of this post-translational modification prevents the development of hypertension. Accordingly, targeting of ACE2 ubiquitination provides a new treatment strategy to reduce hypertension.