tetano
Editor, Senior Moderator
Sci Rep
. 2025 Dec 3.
doi: 10.1038/s41598-025-30304-x. Online ahead of print. Telmisartan reduces systemic inflammation and alters the renin-angiotensin system in mild COVID-19
Angela Lu[SUP] 1 [/SUP], Melissa Agsalda-Garcia[SUP] 2 [/SUP], Weiyuan Hu[SUP] 1 [/SUP], Catherine Chester[SUP] 1 [/SUP], Aditya Anil Naik[SUP] 1 [/SUP], Brooks I Mitchell[SUP] 2 [/SUP], Isaac Asante[SUP] 3 [/SUP], Scott A Souza[SUP] 2 [/SUP], Kuo-Chiang Lian[SUP] 2 [/SUP], Zao Zhang[SUP] 2 [/SUP], Hannah V Schmitz[SUP] 2 [/SUP], Malia L Ramirez[SUP] 2 [/SUP], Richa Varshney[SUP] 2 [/SUP], Serena DelMundo[SUP] 2 [/SUP], Dominic C Chow[SUP] 2 [/SUP], Cecilia M Shikuma[SUP] 2 [/SUP], Stan G Louie[SUP] 4 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a respiratory viral infection that disrupts renin angiotensin system (RAS) peptide metabolism by downregulating angiotensin converting enzyme-II (ACE2), leading to accumulation of pro-inflammatory angiotensin II (AngII). We posit that angiotensin receptor blockers (ARBs) like telmisartan (TEM) can activate the pro-resolving arm of RAS (MasR/ACE2/Ang1-7), reducing lung inflammation in COVID-19 patients. In this randomized, double-blinded, placebo-controlled pilot clinical trial, outpatient SARS-CoV-2-infected study participants received either 40 mg TEM or placebo once daily. Plasma inflammatory biomarker levels revealed a reduction in global systemic inflammation with TEM treatment, corresponding with an increase in MasR. We corroborated these clinical findings with in vitro analysis. A549-ACE2 lung epithelial cells treated with TEM showed increased ACE2 and MasR, as well as decreased angiotensin II receptor type I (AT1R) and angiotensin II receptor type II (AT2R) expression levels. Additionally, AngII peptide levels decreased, while Ang(1-9) and Ang(1-7) increased. TEM treatment at physiologically achievable concentration reduced SARS-CoV-2 viral load. Taken collectively, these results show TEM mediated activation of the Ang(1-7)/MasR/ACE2 pro-resolving arm of RAS, which activates anti-inflammatory events that reduce global inflammation. These findings support the use of ARBs like TEM in mitigating COVID-19 driven alterations in RAS.
. 2025 Dec 3.
doi: 10.1038/s41598-025-30304-x. Online ahead of print. Telmisartan reduces systemic inflammation and alters the renin-angiotensin system in mild COVID-19
Angela Lu[SUP] 1 [/SUP], Melissa Agsalda-Garcia[SUP] 2 [/SUP], Weiyuan Hu[SUP] 1 [/SUP], Catherine Chester[SUP] 1 [/SUP], Aditya Anil Naik[SUP] 1 [/SUP], Brooks I Mitchell[SUP] 2 [/SUP], Isaac Asante[SUP] 3 [/SUP], Scott A Souza[SUP] 2 [/SUP], Kuo-Chiang Lian[SUP] 2 [/SUP], Zao Zhang[SUP] 2 [/SUP], Hannah V Schmitz[SUP] 2 [/SUP], Malia L Ramirez[SUP] 2 [/SUP], Richa Varshney[SUP] 2 [/SUP], Serena DelMundo[SUP] 2 [/SUP], Dominic C Chow[SUP] 2 [/SUP], Cecilia M Shikuma[SUP] 2 [/SUP], Stan G Louie[SUP] 4 [/SUP]
Affiliations
- PMID: 41339688
- DOI: 10.1038/s41598-025-30304-x
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a respiratory viral infection that disrupts renin angiotensin system (RAS) peptide metabolism by downregulating angiotensin converting enzyme-II (ACE2), leading to accumulation of pro-inflammatory angiotensin II (AngII). We posit that angiotensin receptor blockers (ARBs) like telmisartan (TEM) can activate the pro-resolving arm of RAS (MasR/ACE2/Ang1-7), reducing lung inflammation in COVID-19 patients. In this randomized, double-blinded, placebo-controlled pilot clinical trial, outpatient SARS-CoV-2-infected study participants received either 40 mg TEM or placebo once daily. Plasma inflammatory biomarker levels revealed a reduction in global systemic inflammation with TEM treatment, corresponding with an increase in MasR. We corroborated these clinical findings with in vitro analysis. A549-ACE2 lung epithelial cells treated with TEM showed increased ACE2 and MasR, as well as decreased angiotensin II receptor type I (AT1R) and angiotensin II receptor type II (AT2R) expression levels. Additionally, AngII peptide levels decreased, while Ang(1-9) and Ang(1-7) increased. TEM treatment at physiologically achievable concentration reduced SARS-CoV-2 viral load. Taken collectively, these results show TEM mediated activation of the Ang(1-7)/MasR/ACE2 pro-resolving arm of RAS, which activates anti-inflammatory events that reduce global inflammation. These findings support the use of ARBs like TEM in mitigating COVID-19 driven alterations in RAS.