5.5 Rebalancing the RAAS axes by alamandine
Alamandine, a novel member of the RAAS, is similar to Ang (1-7), with one amino acid difference. Alamandine has an Ala which replaces Asp at position 1 of Ang (1-7)(Villela et al. , 2014). Alamandine binds to the Mas-related G protein-coupled receptor (MrgD), which exerts anti-inflammation and anti-fibrosis via up-regulating of the ACE2/alamandine/MrgD axis(Huang et al. , 2020). Accumulating evidences have demonstrated the alamandine has a profound effect in many diseases, including cardiomyopathy, hypertension and so on(Oliveiraet al. , 2019; Paquette et al. , 2018). For example, administration of alamandine could alleviate the inflammation by decreasing the infiltration of neutrophils and regulating macrophage polarization(de Carvalho et al. , 2019). Meanwhile, alamandine protected rat from myocardial injury by inhibiting NF-κB pathway(Songet al. , 2019). Moreover, alamandine produced endothelial-dependent vasorelaxation in aortic rings of mice and rats(Lautner et al. , 2013) and attenuated arterial remodeling(de Souza-Neto et al. , 2019). Interestingly, alamandine could attenuate hepatic fibrosis by regulating autophagy(Huang et al. , 2020). Furthermore, alamandine level is also detectable in human plasma and elevated in patients with chronic renal failure(Hrenak et al. , 2016). These experimental researches are not enough to support that alamandine could be a therapeutic approach, while the protective effects of alamandine should not be ignored.