Ang-(1-7) treatment attenuates lipopolysaccharide-induced early pulmonary fibrosis

Cao, Yongmei; Liu, Yujing; Shang, Jiawei; Yuan, Ziming; Feng, Ping; Yao, Sijia; Guo, Yong; Li, Yingchuan

doi:10.1038/s41374-019-0289-7

Cited by 34 publications

(33 citation statements)

References 47 publications

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“…Moreover, with its vasodilatory, anti-inflammatory, anti-proliferogenic and antifibrotic effects activation of the ACE-2/Ang (1-7)/AT 2 R/MasR pathway counterbalances the harmful effects of the ACE-1/Ang II/ATR-1 pathway on the lung. A reduced ratio of ACE-1/ACE-2 has been documented in ARDS; furthermore, experimentally ARDS and lung fibrosis can be prevented by administration of Ang (1-7) (Cao et al, 2019), or an ARB (Wösten-Van Asperen et al, 2011), indicating that ACE-2 activation limits pulmonary disease progression. This implies not only that ACEis and ARBs are unlikely to be detrimental in Covid-19 patients, but rather that they will be protective.…”

Section: Ace Inhibitors and Arbs Are Beneficial In Acute Respiratory mentioning

confidence: 99%

Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients

Rossi

Sanga

Barton

2020

eLife

136

129

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The discovery that SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) binds to the angiotensin converting enzyme (ACE)-2, which is highly expressed in the lower airways, explained why SARS-CoV-2 causes acute respiratory distress syndrome (ARDS) and respiratory failure. After this, the news spread that ACEis and ARBs would be harmful in SARS-CoV-2-infected subjects.To the contrary compelling evidence exists that the ACE-1/angiotensin (Ang) II/ATR-1 pathway is involved in SARS-CoV-2-induced ARDS, while the ACE-2/Ang (1-7)/ATR2/MasR pathway counteracts the harmful actions of AngII in the lung. A reduced ACE-1/ACE-2 ratio is, in fact, a feature of ARDS that can be rescued by human recombinant ACE-2 and Ang (1-7) administration, thus preventing SARS-CoV-2-induced damages to the lung. Based on the current clinical evidence treatment with ACE-inhibitors I (ACEis) or angiotensin receptor blockers (ARBs) continues to provide cardiovascular and renal protection in patients diagnosed with COVID-19. Discontinuing these medications may therefore potentially be harmful in this patients population. COVID19 PandemicsThe pandemic proportions of Covid-19 (Coronavirus Disease 2019) from the SARS (Severe Acute Respiratory Syndrome) Coronavirus 2 (CoV-2) infecting a million and killing 47,266 people worldwide as of April 2, has fueled enormous interest in the mechanisms whereby this new coronavirus causes acute respiratory distress syndrome (ARDS) and multiorgan failure. The estimated 79% infection rate from undocumented cases in Covid-19 patients (Li et al., 2020), and the high lethality of the infections, along with its enormous socio-economic impact, emphasise the importance of fully understanding these mechanisms for developing effective treatment strategies.Early in 2020 reports of the full RNA sequence of the SARS-CoV-2 virus highlighted remarkable similarities with the SARS-CoV virus, which was responsible of an outbreak that killed 774 people in 2003(Xu et al., 2020. As the processes whereby the SARS-CoV virus infects the lung cells were already dissected (Kuba et al., 2005), and it was held that SARS-CoV-2 uses identical mechanisms, these discoveries allowed an unprecedented acceleration of knowledge.

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Section: Ace Inhibitors and Arbs Are Beneficial In Acute Respiratory mentioning

confidence: 99%

Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients

Rossi

Sanga

Barton

2020

eLife

136

129

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“…Dos Santos & Sampaio, 2015;Raffai et al,, 2011;Tesanovic et al, 2010Lemos et al, 2005Zhou et al, 2013Hermenegildo et al, 2011 ;Sobrino et al, 2010Sobrino et al, , 2017. Rodgers & di Zerega, 2013;Rodgers et al, 2013Syrov et al, 1997Nakada et al, 2014 Liver protective Lubel et al, 2009 ;Pereira et al, 2007;Li, 2013Suski et al, 2012Shakhmurova et al, 2010aXia et al, 2013bTian et al, 2012 Lung protective Imai et al, 2008;Klein et al, 2013;Uhal et al, 2013;Shenoy et al, 2015 ;Cao et al, 2019Klein et al, 2013Rodrigues-Machado et al, 2013;Cao et al, 2019Wu et al, 1998Li et al, 2013;Song et al, 2019Hamidi et al, 2011Breithaupt-Faloppa et al, 2013 Kidney protective Zhou et al, 2012;Xu et al, 2013;Barroso et al, 2012;Suski et al, 2013 ;Silveira et al, 2010Silveira et al, , 2013Pinheiro et al, 2004. Syrov et al, 1992…”

Section: Vasorelaxantmentioning

confidence: 99%

20-Hydroxyecdysone activates the protective arm of the renin angiotensin system via Mas receptor

Lafont

Raynal

Serova

et al. 2020

Preprint

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20-Hydroxyecdysone (20E) is a steroid hormone that plays a key role in insect development through nuclear ecdysone receptors (EcRs) and at least one membrane GPCR receptor (DopEcR) and displays numerous pharmacological effects in mammals. However, its mechanism of action is still debated, involving either an unidentified GPCR or the estrogen ERβ receptor. The goal of our study was to better understand 20E mechanism of action.A mouse myoblast cell line (C2C12) and the gene expression of myostatin (a negative regulator of muscle growth) was used as a reporter system of anabolic activity. Experiments using protein-bound 20E established the involvement of a membrane receptor. 20E-like effects were also observed with Angiotensin- (1-7), the endogenous ligand of Mas. Additionally, the effect on myostatin gene expression was abolished by Mas receptor knock-down using small interfering RNA (siRNA) or pharmacological inhibitors.17-Estradiol (E2) also inhibited myostatin gene expression, but proteinbound E2 was inactive, and E2 activity was not abolished by angiotensin-(1-7) antagonists. A mechanism involving cooperation between Mas receptor and a membrane-bound palmitoylated estrogen receptor is proposed.The possibility to activate the Mas receptor with a safe steroid molecule is consistent with the pleiotropic pharmacological effects of ecdysteroids in mammals and indeed this mechanism may explain the close similarity between angiotensin-(1-7) and 20E effects. Our findings open a lot of possible therapeutic developments by stimulating the protective arm of the renin-angiotensin-aldosterone system (RAAS) with 20E.

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“…In experimental lipopolysaccharide (LPS)-induced lung fibrosis, Ang II levels were slightly elevated in the plasma and even more increased in the bronchoalveolar lavage fluid. These changes were accompanied by higher AT1R expression in the pulmonary tissue [30]. Similarly, increased Ang II levels were also detected in the serum of patients with avian influenza H5N1 [31].…”

Section: Ras and Pulmonary Diseasesmentioning

confidence: 74%

Renin–Angiotensin System: An Important Player in the Pathogenesis of Acute Respiratory Distress Syndrome

Hrenak

Šimko

2020

IJMS

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Acute respiratory distress syndrome (ARDS) is characterized by massive inflammation, increased vascular permeability and pulmonary edema. Mortality due to ARDS remains very high and even in the case of survival, acute lung injury can lead to pulmonary fibrosis. The renin–angiotensin system (RAS) plays a significant role in these processes. The activities of RAS molecules are subject to dynamic changes in response to an injury. Initially, increased levels of angiotensin (Ang) II and des-Arg9-bradykinin (DABK), are necessary for an effective defense. Later, augmented angiotensin converting enzyme (ACE) 2 activity supposedly helps to attenuate inflammation. Appropriate ACE2 activity might be decisive in preventing immune-induced damage and ensuring tissue repair. ACE2 has been identified as a common target for different pathogens. Some Coronaviruses, including SARS-CoV-2, also use ACE2 to infiltrate the cells. A number of questions remain unresolved. The importance of ACE2 shedding, associated with the release of soluble ACE2 and ADAM17-mediated activation of tumor necrosis factor-α (TNF-α)-signaling is unclear. The roles of other non-classical RAS-associated molecules, e.g., alamandine, Ang A or Ang 1–9, also deserve attention. In addition, the impact of established RAS-inhibiting drugs on the pulmonary RAS is to be elucidated. The unfavorable prognosis of ARDS and the lack of effective treatment urge the search for novel therapeutic strategies. In the context of the ongoing SARS-CoV-2 pandemic and considering the involvement of humoral disbalance in the pathogenesis of ARDS, targeting the renin–angiotensin system and reducing the pathogen’s cell entry could be a promising therapeutic strategy in the struggle against COVID-19.

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Ang-(1-7) treatment attenuates lipopolysaccharide-induced early pulmonary fibrosis

Cited by 34 publications

References 47 publications

Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients

Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients

20-Hydroxyecdysone activates the protective arm of the renin angiotensin system via Mas receptor

Renin–Angiotensin System: An Important Player in the Pathogenesis of Acute Respiratory Distress Syndrome

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