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).