New Cardiovascular and Pulmonary Therapeutic Strategies Based on the Angiotensin-Converting Enzyme 2/Angiotensin-(1–7)/Mas Receptor Axis

Ferreira, Anderson J.; Murça, Tatiane M.; Fraga-Silva, Rodrigo A.; Castro, Carlos Henrique; Raizada, Mohan K.; Santos, Robson A. S.

In the past few years, the participation of the ACE2/Ang-(1-7)/Mas axis in the establishment and progression of pulmonary diseases has become evident. Indeed, the important role of the RAS in the lung pathophysiology and the side effects and pulmonary toxicity induced by the ACEi raised the interest to evaluate the activation of the ACE2/Ang-(1-7)/Mas axis as an alternative target to treat pulmonary pathologies. Thus, it has been reported beneficial outcomes induced by the activation of this axis in animal models of acute respiratory distress syndrome (ARDS), pulmonary hypertension (PH), fibrosis, and lung cancer [31, 37, [114] [115] [116] [117] . These studies pointed out that the imbalance between the ACE/Ang II/AT 1 and the ACE2/Ang-(1-7)/Mas axes of the RAS might be relevant in lung diseases. Taking into account that systemic hypotension is an important limitation to the use of ACEi and ARBs in pulmonary patients, therapies based on the ACE2/Ang-(1-7)/Mas axis emerge as a safe and efficient approach since studies using the ACE2 activator XNT or ACE2 gene transfer have shown that these strategies induce beneficial pulmonary outcome without changes in systemic blood pressure in rats and mice [39, 117, 118] .