5.4 Rebalancing the RAAS axes by Ang (1-7)
Our previous studies showed that Ang (1-7) exerts inhibitory effects on inflammation and oxidation via activating the ACE2/Ang (1-7)/MasR axis and inhibiting the ACE/Ang Ⅱ/AT1R axis(Cai et al. , 2016; Menget al. , 2015). Ang (1-7)-induced signaling have been clarified in several aspects. The increase in NO release is the most classic aspect related to the protective role of Ang (1-7) and includes calcium-independent pathways and the posttranslational regulation of endothelial nitric oxide synthase (eNOS)(Sampaio et al. , 2007). Ang (1-7) additionally decreases TGF-β/NF-kB signaling, a key pathway in inflammation(Marcus et al. , 2013). For example, Ang (1-7) significantly attenuated the peritonitis-induced sepsis via suppressing inflammation and apoptosis(Tsai et al. , 2018). Meanwhile, upregulation the ACE2/Ang (1-7)/MasR axis could ameliorate sepsis-induced acute lung injury(Chen et al. , 2019). Furthermore, administration of Ang (1-7) significantly reduced the neutrophil recruitment and modulated the inflammation in IBD(Khajah et al. , 2017). Additionally, Ang (1-7) has been proved that pretreatment could attenuate the Ang Ⅱ-induced renal injury via Mas receptor(Kim et al. , 2015). Furthermore, the loose interstitial fibrosis was presented in lung tissue of COVID-19 patient, indicated the clinician should pay more attention to the pulmonary fibrosis(Zhang et al. , 2020). In coincidence, Ang (1-7) also exerts protective effects against fibrosis. We found that Ang (1-7) alleviated pulmonary fibrosis by inhibiting NOX4-derived ROS-mediated RhoA/Rock pathway(Meng et al. , 2015). The similar effects could be found in liver fibrosis(Cai et al. , 2016). The above compelling evidence indicated that the Ang (1-7) may represent novel therapeutic approach in the treatment of COVID-19.