Key result
ACE2-Ang 1-7-Mas axis exerts protective counterregulatory effects against hypoxic cardiopulmonary injury.
Why the study?
Hypoxia is a prominent factor influencing alternative RAS branches, but the mechanisms behind diverse hypoxic insults on alternative RAS activity across different durations, tissues, and clinical contexts needed comprehensive review.
The alternative RAS axis (ACE2/Ang(1-7)/Mas receptor) represents a key counter-regulatory mechanism in hypoxic conditions like myocardial infarction and COVID-19, offering potential diagnostic and therapeutic targets.
Answers are grounded in this paper and cite their sources.
Supports ACE2/Ang(1-7)/Mas protection in hypoxic CV/pulmonary injury; hypothesis-generating for targeted therapies pending prospective trials.
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.
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Rajtík et al. (2021) conducted a review in Hypoxia-associated cardiovascular and cardiopulmonary diseases. ACE2/Ang(1-7)/Mas axis modulation was evaluated. The alternative ACE2/Ang(1-7)/Mas axis of the renin-angiotensin system exerts counterregulatory protective effects against hypoxic injuries in cardiovascular and pulmonary conditions.
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