While it is quite clear that cell-bound ACE2 and the counter-regulatory ACE2/Ang-(1-7)/MASR axis plays a protective role in inflammation and cardiovascular diseases [125], elevated ACE2 levels in plasma rather seem to a have a negative impact and could be indirectly related to an overactivation of the classical ACE/AngII/AT1R axis in the local RAS. This evidence concerns the gene ACE2 and cardiovascular disorder.