key: cord-0740431-8cisizxh
authors: Motta‐Santos, Daisy; Santos, Robson A S; Santos, Sérgio Henrique Sousa
title: Angiotensin‐(1‐7) and Obesity: Role on cardiorespiratory fitness and COVID‐19 implications
date: 2020-07-04
journal: Obesity (Silver Spring)
DOI: 10.1002/oby.22949
sha: 33470a0c7547b260a0a5187fcd128ec32d83afe3
doc_id: 740431
cord_uid: 8cisizxh

We have read with interest the recent review by Zbinden‐Foncea et.al., suggesting that high levels of cardiorespiratory fitness induced by prior exercise training may confer some innate immune‐protection against Covid‐19 by attenuating the “cytokine storm syndrome” by modulating angiotensin‐converting enzyme 2 (ACE2) effects. However, it is important to highlight that the benefic effects of physical exercise also involves the Ang‐(1‐7)/Mas axis activation.

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We have read with interest the recent review by Zbinden-Foncea et.al., suggesting that high levels of cardiorespiratory fitness induced by prior exercise training may confer some innate immune-protection against Covid-19 by attenuating the "cytokine storm syndrome" by modulating angiotensin-converting enzyme 2 (ACE2) effects 1 . However, it is important to highlight that the benefic effects of physical exercise also involves the Ang-(1-7)/Mas axis activation.

Angiotensin-(1-7) anti-inflammatory actions have been described for more than 10 years 2 being produced by human vascular endothelium 3 . Arterial hypertension, asthma, diabetes and obesity are some of the chronic diseases associated with Ang-(1-7)/Mas axis unbalance 2,4 . These persistent conditions are all improved by angiotensin-(1-7) or its homologues treatments. The beneficial mechanisms are correlated with improved inflammation resolution, protection against endotoxin induced muscle wasting 5 , TLR4 activation and NF-Kb pathway modulation 6 . Physical training also promotes similar anti-inflammatory effects, which could be complementary or additive.

Recent studies suggest that physical training is able to modulate the renin-angiotensin system, including the ACE2 expression and activity. Some important data have shown that the SARS-CoV-2 binding with ACE2 promotes its internalization 7 , which partially prevents Ang-(1-7)

formation from ACE2. The Ang-(1-7) down production could be associated with COVID-19

complications. Some clinical studies showed that the ACE inhibitors (iACE) and AT1 blockers (BRA) use could be beneficial in the clinical outcomes of hypertensive patients or those with SARS-CoV-2 infection 7 . It is important to note that these antihypertensive agents acts by direct modulation of the renin-angiotensin system (RAS), as well as observed in response to physical training.

Recent publications suggested the Ang-(1-7) use on treating COVID-19 features 8 

This article is protected by copyright. All rights reserved Genetic deletion of ACE2 in mice decrease physical performance 9 and MAS receptor mediates cardiac and metabolic adaptations induced by physical training 10 . Therefore, it is important to highlight that the possible protective effects of physical training may involve the mainstream actions of the ACE2/Ang-(1-7)/Mas axis.

The Ang-(1-7) receptor (MAS) lack is also associated with several changes in the immune and metabolic system demonstrating its importance and participation in anti-inflammatory protection and resolution of inflammation 2, 4 . Recently, a study demonstrated that people with obesity and arterial hypertension preterm adolescents have reduced levels of Ang-(1-7).

Metabolic syndrome, aging, obesity, diabetes, hypertension and some other cardiometabolic chronic diseases have been described as risk factors for severe complications and mortality in COVID-19 patients. All these persistent disorders have also been described to be improved by Authors Disclosure:

Does high cardiorespiratory fitness confer some protection against pro-inflammatory responses after infection by SARS-CoV-2? Obesity (Silver Spring)

Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity

The ACE2/Angiotensin

Endotoxin-induced skeletal muscle wasting is prevented by angiotensin (1-7) through a p38 MAPK dependent mechanism

Oral Angiotensin-(1-7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-kappaB in rats fed with high-fat diet

Substituting Angiotensin-(1-7) to Prevent Lung Damage in SARS-CoV-2 Infection?

The authors state that there are no conflicts of interests considering this paper publication.

The present study was partially supported by grants from FAPEMIG, CAPES, and CNPq.

This article is protected by copyright. All rights reserved