8.2 Ang-(1-7) and viral infections
Recent studies have shed light on the involvement of the Renin-Angiotensin System (RAS) in the pathogenesis of various viral infections. Specifically, in models of Influenza A infection caused by strains such as H7N9 and H5N1, the deficiency of angiotensin-converting enzyme 2 (ACE2), which is responsible for converting Angiotensin II (AngII) into Ang-(1-7), has been shown to intensify the pathogenesis and lead to acute lung injury (ALI) associated with increased morbidity. Absence of ACE2 results in an increase in inflammation, primarily due to the activation of the Type 1 receptor (AT1R) by AngII. This dysregulation of the ACE2/Ang-(1-7)/AT1R axis contributes to the exacerbation of lung inflammation and injury in response to Influenza A infection (Zou et al., 2014). Interestingly, administration of ACE2 has been found to improve acute inflammation caused by Influenza A (H5N1) infection, suggesting a potential therapeutic approach (Zou et al., 2014). In patients with severe influenza A (H7N9) infection, an elevation in plasma levels of AngII has been observed and strongly associated with disease progression (Yang et al., 2014). This further supports the notion that dysregulation of the RAS system, specifically an imbalance between AngII and Ang-(1-7), contributes to the severity of viral infections and their associated inflammatory responses. These findings highlight the importance of the RAS system in viral infection pathogenesis and suggest that modulation of this system, such as restoring the balance between AngII and Ang-(1-7), may have therapeutic potential in mitigating the inflammatory response and improving outcomes in severe viral infections. However, further research is needed to fully understand the complex interactions between the RAS system and viral infections and to explore the potential of targeting this system for therapeutic interventions.
In addition to AngII, studies have evaluated the relevance of Ang-(1-7) and its Mas receptor. Our observations revealed that oral administration of Ang-(1-7) reduced mortality and attenuated excessive inflammation by promoting resolution effects such as apoptosis and efferocytosis of neutrophils following Influenza A (H1N1) infection. These effects were associated with a decrease in viral load and lung injury. Importantly, the success of Ang-(1-7) treatment was directly linked to the presence of the Mas receptor, as the absence of this receptor worsened the infection, leading to 100% mortality (Melo et al., 2021).