APLN and heart failure: Apelin has been shown to increase ACE2 levels in the failing heart and to couple apelin to RAS [143], and it is interesting to add that the activation of the Apelin-ACE 2 pathway has been proposed as a mechanism for the beneficial effects of the sodium–glucose cotransporter-2 (SGLT2) inhibitor canagliflozin in a model of hypertrophy and heart failure in salt-sensitive rats [144].