ArticleClinical science (London, England : 1979)2021
Experimental data using candesartan and captopril indicate no double-edged sword effect in COVID-19.
Article in Clinical science (London, England : 1979), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- The rationale for the treatment of long-Covid symptoms - A cardiologist's view.Frontiers in cardiovascular medicine · 2022Pooled it
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- METTL3 mediates mJournal of advanced research · 2026Article
- Stalling the Enemy: Targeting Nsp13 for Next-Generation SARS-CoV-2 Antivirals.International journal of molecular sciences · 2026Article
- Unlocking Novel Therapeutic Potential of Angiotensin II Receptor Blockers.International journal of molecular sciences · 2025Review
- Synthesis and Inhibitory Assessment of ACE2 Inhibitors for SARS-CoV-2: AnThe Journal of organic chemistry · 2025Article
- Article
- Non-HLA angiotensin-type-1 receptor autoantibodies mediate the long-term loss of grafted neurons in Parkinson's disease models.Stem cell research & therapy · 2024Article
- The role of the brain renin-angiotensin system in Parkinson´s disease.Translational neurodegeneration · 2024Review
- Potential Target Discovery and Drug Repurposing for Coronaviruses: Study Involving a Knowledge Graph-Based Approach.Journal of medical Internet research · 2023Article
- Review
- Organ and cell-specific biomarkers of Long-COVID identified with targeted proteomics and machine learning.Molecular medicine (Cambridge, Mass.) · 2023Article
- An overview on the treatments and prevention against COVID-19.Virology journal · 2023Review
- Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: Multilayered cross-talks in the setting of coinfections and comorbidities.PLoS pathogens · 2023Review
- COVID-19, obesity, and immune response 2 years after the pandemic: A timeline of scientific advances.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Review
- Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease.NPJ Parkinson's disease · 2022Article
- Adamalysins in COVID-19 - Potential mechanisms behind exacerbating the disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Role of the renin-angiotensin system in NETosis in the coronavirus disease 2019 (COVID-19).Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment.Biomedicines · 2022Review
- Potential of Endogenous Oxytocin in Endocrine Treatment and Prevention of COVID-19.Frontiers in endocrinology · 2022Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The key link between renin-angiotensin system (RAS) and COVID-19 is ACE2 (angiotensin-converting enzyme 2), which acts as a double-edged sword, because ACE2 increases the tissue anti-inflammatory response but it is also the entry receptor for the virus. There is an important controversy on several drugs that regulate RAS activity and possibly ACE2, and are widely used, particularly by patients most vulnerable to severe COVID-19. In the lung of healthy rats, we observed that candesartan (an angiotensin type-1, AT1, receptor blocker; ARB) and captopril (an ACE inhibitor; ACEI) up-regulated expression of tissue ACE2 and RAS anti-inflammatory axis receptors (AT2 and Mas receptors). This effect was particularly pronounced in rats with metabolic syndrome (obesity, increased blood pressure and hyperglycemia) and aged rats. Treatment of cultures of human type-II pneumocytes with candesartan or captopril induced up-regulation of ACE2 expression in cells. Treatment with viral spike protein induced a decrease in full-length (i.e. transmembrane) ACE2, an increase in levels of a short intracellular ACE2 polypeptide and an increase in ADAM17 activity in cells, together with an increase in levels of soluble ACE2 and major proinflammatory cytokines in the culture medium. Spike protein-induced changes and levels of spike protein internalization in cells were inhibited by pretreatment with the above-mentioned drugs. The results suggest that these drugs increase ACE2 levels and promote the anti-inflammatory RAS axis in the lung. Furthermore, possible up-regulation of viral entry by the drug-induced increase in expression of transmembrane ACE2 is counteracted by additional mechanisms, particularly by drug-induced inhibition of ADAM17 activity.
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