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The effect of renin-angiotensin-aldosterone system inhibitors on organ-specific ace2 expression in zebrafish and its implications for COVID-19.
Kim, Gha-Hyun J; Melgoza, Adam; Jiang, Fei; Guo, Su.
  • Kim GJ; Department of Bioengineering and Therapeutic Sciences and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, San Francisco, CA, 94158, USA. Jeffrey.kim@ucsf.edu.
  • Melgoza A; Graduate Program of Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, CA, 94158, USA. Jeffrey.kim@ucsf.edu.
  • Jiang F; Department of Bioengineering and Therapeutic Sciences and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, San Francisco, CA, 94158, USA.
  • Guo S; Graduate Program of Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, CA, 94158, USA.
Sci Rep ; 11(1): 23670, 2021 12 08.
Article in English | MEDLINE | ID: covidwho-1560986
ABSTRACT
Among cases of SARS-CoV-2 infections that result in serious conditions or death, many have pre-existing conditions such as hypertension and are on renin-angiotensin-aldosterone system (RAAS) inhibitors. The angiotensin-converting-enzyme-2 (ACE2), a key protein of the RAAS pathway, also mediates cellular entry of SARS-CoV-2. RAAS inhibitors might affect the expression levels of ace2, which could impact patient susceptibility to SARS-CoV-2. However, multi-organ-specific information is currently lacking and no species other than rodents have been examined. To address this knowledge gap, we treated adult zebrafish with the RAAS inhibitors aliskiren, olmesartan, and captopril for 7 consecutive days and performed qRT-PCR analysis of major RAAS pathway genes in the brain, gill, heart, intestine, kidney, and liver. Both olmesartan and captopril significantly increased ace2 expression in the heart, gill, and kidney. Olmesartan also increased ace2 expression in the intestine. Conversely, aliskiren significantly decreased ace2 expression in the heart. Discontinuation of compound treatments for 7 days did not return ace2 expression to baseline levels. While potential risks or benefits of antihypertensive RAAS inhibitors to SARS-CoV-2 infections in humans remain uncertain, this study provides new insights regarding the impact of RAAS inhibitors on organ-specific ace2 expression in another vertebrate model, thereby providing comparative data and laying scientific groundwork for future clinical decisions of RAAS inhibitor use in the context of COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Zebrafish / Angiotensin-Converting Enzyme Inhibitors / Down-Regulation / Up-Regulation / Angiotensin-Converting Enzyme 2 Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-03244-5

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Zebrafish / Angiotensin-Converting Enzyme Inhibitors / Down-Regulation / Up-Regulation / Angiotensin-Converting Enzyme 2 Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-03244-5