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Review
. 2021 Nov 26;22(23):12800.
doi: 10.3390/ijms222312800.

Alternative RAS in Various Hypoxic Conditions: From Myocardial Infarction to COVID-19

Tomas Rajtik  1 , Peter Galis  1 , Linda Bartosova  1 , Ludovit Paulis  2 , Eva Goncalvesova  3 , Jan Klimas  1
Affiliations
Review

Alternative RAS in Various Hypoxic Conditions: From Myocardial Infarction to COVID-19

Tomas Rajtik et al. Int J Mol Sci. .

Abstract

Alternative branches of the classical renin-angiotensin-aldosterone system (RAS) represent an important cascade in which angiotensin 2 (AngII) undergoes cleavage via the action of the angiotensin-converting enzyme 2 (ACE2) with subsequent production of Ang(1-7) and other related metabolites eliciting its effects via Mas receptor activation. Generally, this branch of the RAS system is described as its non-canonical alternative arm with counterbalancing actions to the classical RAS, conveying vasodilation, anti-inflammatory, anti-remodeling and anti-proliferative effects. The implication of this branch was proposed for many different diseases, ranging from acute cardiovascular conditions, through chronic respiratory diseases to cancer, nonetheless, hypoxia is one of the most prominent common factors discussed in conjugation with the changes in the activity of alternative RAS branches. The aim of this review is to bring complex insights into the mechanisms behind the various forms of hypoxic insults on the activity of alternative RAS branches based on the different duration of stimuli and causes (acute vs. intermittent vs. chronic), localization and tissue (heart vs. vessels vs. lungs) and clinical relevance of studied phenomenon (experimental vs. clinical condition). Moreover, we provide novel insights into the future strategies utilizing the alternative RAS as a diagnostic tool as well as a promising pharmacological target in serious hypoxia-associated cardiovascular and cardiopulmonary diseases.

Keywords: angiotensin(1-7); angiotensin-converting enzyme 2; hypoxia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
RAS cleavage cascade and the principal receptors of Ang II and Ang(1-7).
Figure 2
Figure 2
Selected molecular pathways affected by ACE2/Ang(1-7)/Mas axis in cardiovascular and pulmonary systems.
Figure 3
Figure 3
The main conclusions of the overall ACE2/Ang(1-7)/Mas axis activity in cardiovascular and pulmonary hypoxic conditions.
See this image and copyright information in PMC

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