Emergence and evolution of the renin-angiotensin-aldosterone system
Open accessAbstract
The renin-angiotensin-aldosterone system (RAAS) is not the sole, but perhaps the most important volume regulator in vertebrates. To gain insights into the function and evolution of its components, we conducted a phylogenetic analysis of its main related genes. We found that important parts of the system began to appear with primitive chordates and tunicates and that all major components were present at the divergence of bony fish, with the exception of the Mas receptor. The Mas receptor first appears after the bony-fish/tetrapod divergence. This phase of evolutionary innovation happened about 400 million years ago. We found solid evidence that angiotensinogen made its appearance in cartilage fish. The presence of several RAAS genes in organisms that lack all the components shows that these genes have had other ancestral functions outside of their current role. Our analysis underscores the utility of sequence comparisons in the study of evolution. Such analyses may provide new hypotheses as to how and why in today's population an increased activity of the RAAS frequently leads to faulty salt and volume regulation, hypertension, and cardiovascular diseases, opening up new and clinically important research areas for evolutionary medicine.
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Because BIO101 does not interfere with AT1R like TRV-027, the positive results in COVID-19 suggest a particular importance of MasR activation in the regulation of respiratory function.
“Because BIO101 does not interfere with AT1R like TRV-027, our positive results in COVID-19 perhaps suggest a particular importance of MasR activation in the regulation of respiratory function.28”
The role of the RAS in COVID-19 pathophysiology may be more complex than previously thought.
“Our results, and those of other clinical studies, suggests that the role of the RAS in COVID-19 pathophysiology may be more complex than previously thought.9,28”
The contrasting results between the effect of BIO101 and of other compounds may be explained by the complexity of the RAS.
“These contrasting results between the effect of BIO101 and of these other compounds may be explained by the complexity of the RAS composed of many proteases, receptors and peptidic ligands with often opposing effects.28”
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- Authors
- Fournier, D., Luft, F. C., Bader, M., Ganten, D., & Andrade-Navarro, M. A.
- Affiliations
- Max Delbrück Center (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Corresponding author
- Andrade-Navarro, Miguel A.
- Venue
- Journal of Molecular Medicine
- Published
- 2012-04-14
- Volume
- 90
- Issue
- 5
- Pages
- 495-508
- ISSN
- 0946-2716 (ISSN-L)
- 1432-1440
- PMC
- PMC3354321
- OpenAlex
- W2086052108
- Cited by
- 165
- References
- 60
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 12 · 2023: 11 · 2022: 15 · 2021: 18 · 2020: 23 · 2019: 12 · 2018: 15 · 2017: 4 · 2016: 11 · 2015: 9 · 2014: 12 · 2013: 12 · 2012: 2
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Journal of Molecular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- renin-angiotensin-aldosterone system, phylogenetic analysis, angiotensinogen, Mas receptor, angiotensin II receptor, volume regulation, water-salt balance, Chordata, tunicates, Chondrichthyes, bony fishes, tetrapods, evolutionary innovation, hypertension, cardiovascular disease, evolutionary medicine
- MeSH terms
- Animals, Humans, Phylogeny, Renin-Angiotensin System, Time Factors, Sequence Homology, Amino Acid, Sequence Analysis, DNA, Evolution, Molecular
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