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The Counter-Regulatory Renin-Angiotensin System: A Surprising Ally in the Field of COVID-19
Mariali Palacios Cruz1, Jairo Castellar-Lopez1, Juan Manuel Pretelt2
1Grupo de Investigación Avanzada en Biomedicina, Faculty of Health, Exact and Natural Sciences, Universidad Libre Seccional Barranquilla, Barranquilla, Colombia.
Introduction:
Over the past four years, SARS-CoV-2 and COVID-19 have become global health crises, spurring extensive research on virus behavior, complications, and treatments. The virus interacts with a component of the renin-angiotensin system (RAS), altering inflammatory, hypertrophic, and hemodynamic responses via binding to ACE2 found in organs like the heart, lungs, and kidneys.
Objective:
This review explores the RAS-COVID-19 interplay, focusing on key molecules like ACE2, Ang-(1-7), and Ang-(1-9), influencing susceptibility, severity, and treatments. It seeks to clarify ACE2's dual role in viral entry and protection and assess the therapeutic potential of balancing Ang-(1-7) and Ang-(1-9) to prevent disease progression and related complications.
Methods:
Studies were chosen through a systematic search in databases, such as PubMed, Scopus, and Web of Science. The inclusion criteria were centered on peer-reviewed research that explored the relationship between SARS-CoV-2 and important RAS molecules, including ACE2, Ang-(1-7), and Ang-(1-9), seeking information on therapies, severity, and susceptibility. Non-peer-reviewed articles and those lacking focus on RAS-COVID-19 interplay were excluded. Titles and abstracts were screened, followed by full-text assessment and data extraction for analysis.
Results:
Some studies indicate that the peptides Ang-(1-7) and Ang-(1-9) could provide protective effects against heart-related complications by counteracting the harmful impacts of the angiotensin II pathway, which is often exacerbated by SARS-CoV-2. Ang-(1-7) and Ang-(1-9) are recognized for promoting vasodilation, reducing inflammation, and preventing fibrosis, which can mitigate the heart damage typically associated with COVID-19.
Discussion:
ACE2, a component of the non-canonical RAS, is closely linked to SARS-CoV-2 and plays a pivotal role in the pathophysiology of COVID-19. Ang-(1-9) and Ang-(1-7) are produced by ACE2 and have demonstrated positive cardiovascular effects. In the context of COVID-19, Ang-(1- 7) has shown protective effects in preclinical studies and clinical trials; however, more evidence is needed to support this effect.
Conclusion:
Further research, including clinical trials, is vital to understand and develop precise therapies for COVID-19 and similar infectious diseases.
Insights
This review explores the renin-angiotensin system (RAS) and COVID-19 interaction, highlighting ACE2's role. Angiotensin-(1-7) and Angiotensin-(1-9) show potential in mitigating cardiovascular complications from SARS-CoV-2 infection.
Area of Science:
- Cardiovascular Research
- Infectious Disease Epidemiology
- Molecular Biology
Background:
- SARS-CoV-2 (the virus causing COVID-19) has led to global health crises, prompting research into its mechanisms.
- The virus interacts with the renin-angiotensin system (RAS), affecting inflammatory and hemodynamic responses through ACE2 binding in organs like the heart and lungs.
Purpose of the Study:
- To review the interplay between the RAS and COVID-19, focusing on key molecules like ACE2, Angiotensin-(1-7), and Angiotensin-(1-9).
- To clarify ACE2's dual role in viral entry and protection.
- To assess the therapeutic potential of modulating Angiotensin-(1-7) and Angiotensin-(1-9) levels to prevent disease progression and complications.
Main Methods:
- Systematic literature search in PubMed, Scopus, and Web of Science.
- Inclusion of peer-reviewed studies on SARS-CoV-2 and RAS molecules (ACE2, Angiotensin-(1-7), Angiotensin-(1-9)).
- Exclusion of non-peer-reviewed articles and those not focused on the RAS-COVID-19 interplay.
Main Results:
- Studies suggest Angiotensin-(1-7) and Angiotensin-(1-9) may protect against COVID-19-related heart complications by counteracting the angiotensin II pathway.
- These peptides promote vasodilation, reduce inflammation, and prevent fibrosis, potentially mitigating cardiac damage.
Conclusions:
- ACE2 is integral to COVID-19 pathophysiology, linking the non-canonical RAS to SARS-CoV-2.
- Angiotensin-(1-7) and Angiotensin-(1-9), produced by ACE2, exhibit cardioprotective effects.
- While preclinical and some clinical data support Angiotensin-(1-7)'s protective role in COVID-19, further clinical trials are necessary.
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