Targeting the renin–angiotensin system as novel therapeutic strategy for pulmonary diseases

Tan, W.S. Daniel; Liao, Wupeng; Zhou, Shuo; Mei, Dan; Wong, W.S. Fred

doi:10.1016/j.coph.2017.12.002

Cited by 159 publications

(152 citation statements)

References 49 publications

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“…44 Restoration of ACE2 through the administration of recombinant ACE2 appeared to reverse this devastating lung-injury process in preclinical models of other viral infections 49,50 and safely reduced angiotensin II levels in a phase 2 trial evaluating acute respiratory distress syndrome in humans. 51 Dysregulated ACE2 may theoretically also attenuate cardioprotection in the context of myocardial involvement and abnormal pulmonary hemodynamics 52,53 in Covid-19. Markers of myocardial injury have been shown to be elevated during the disease course of Covid-19 54 and to increase rapidly with clinical deterioration and preceding death.…”

Section: P Otential For Benefit R Ather Than Harm Of R a A S Blockersmentioning

confidence: 99%

Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19

et al. 2020

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Section: P Otential For Benefit R Ather Than Harm Of R a A S Blockersmentioning

confidence: 99%

Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19

et al. 2020

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“…The RAS pathway consists of a cascade of proteases producing some bioactive molecules [1]. Angiotensinogen is mainly released by the liver and then cleaved by renin, which is secreted by the juxtaglomerular cells in the kidney, thus generating the decapeptide angiotensin I (Ang I) [2,3]. Ang I is converted to angiotensin II (Ang II) by angiotensin-converting enzymes (ACE), expressed by the endothelial cells of several organs, such as lung, heart, kidney, and brain [4,5].…”

Section: The Physiological Basis Of Rasmentioning

confidence: 99%

“…Therefore, the equilibrium point of the RAS is represented by Ang II, which can also be converted into heptapeptide Ang-(1-7) thanks to the action of angiotensin-converting enzyme 2 (ACE2). Ang- (1)(2)(3)(4)(5)(6)(7), which can also be generated by the cleavage of ANG I by endopeptidases, and binds Mas receptors counteracting most of the deleterious actions of the ACE/Ang II/AT1 axis, especially in pathological conditions [10,11].…”

Section: The Physiological Basis Of Rasmentioning

confidence: 99%

COVID-19 and RAS: Unravelling an Unclear Relationship

D’Ardes

Boccatonda

Rossi

et al. 2020

IJMS

105

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The renin-angiotensin system (RAS) plays a main role in regulating blood pressure and electrolyte and liquid balance. Previous evidence suggests that RAS may represent an important target for the treatment of lung pathologies, especially for acute respiratory distress syndrome and chronic fibrotic disease. The scientific community has recently focused its attention on angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor 1 (AT1R) inhibitors and their possible benefit/harms for patients infected by Coronavirus disease (COVID-19) who experience pneumonia, but there are still some doubts about the effects of these drugs in this setting.

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“…In lung fibrosis induced by smoking, Ang-(1-7) reduced the hydrogen peroxide concentration, protein levels of NOX4 and impairment of autophagy (Pan et al, 2018). Therefore, inhibition of the upstream ACE-Ang II-AT 1 pathway and activation of the downstream ACE2-Ang-(1-7)-Mas pathway are two feasible strategies demonstrating efficacy in various pulmonary disease models (Tan, Liao, Zhou, Mei, & Wong, 2018).…”

Section: Discussionmentioning

confidence: 99%

Interaction of N‐acetyl‐seryl‐aspartyl‐lysyl‐proline with the angiotensin‐converting enzyme 2–angiotensin‐(1–7)–Mas axis attenuates pulmonary fibrosis in silicotic rats

Gao

Zhang

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?What are the effects of the antifibrotic peptide acetyl‐seryl‐aspartyl‐lysyl‐proline (Ac‐SDKP) on the angiotensin‐converting enzyme 2 (ACE2)–angiotensin‐(1–7)–Mas axis during the occurrence and progression of silicosis? What is the main finding and its importance?Ac‐SDKP inhibited lung fibrosis in rats exposed to silica by activation of the ACE2–angiotensin‐(1–7)–Mas axis. Angiotensin‐(1–7) potentially promotes Ac‐SDKP by increasing the level of meprin α, the major synthetase of Ac‐SDKP. Thus, the interaction Ac‐SDKP and angiotesin‐(1–7) in silicosis could provide a new therapeutic strategy. Abstract The central role of angiotensin‐converting enzyme (ACE) in the occurrence and progression of silicosis has been established. The antifibrotic peptide acetyl‐seryl‐aspartyl‐lysyl‐proline (Ac‐SDKP) can be degraded by ACE. The ACE2–angiotensin‐(1–7)–Mas axis is protective and acts to counterbalance the detrimental effects of ACE–angiotensin II (Ang II)–Ang II type 1 receptor and exerts antifibrotic effects. Here, we demonstrate an interaction between Ac‐SDKP and Ang‐(1–7) in the inhibition of collagen deposition and myofibroblast differentiation in rats exposed to silica. Treatment with Ac‐SDKP increased the level of ACE2–Ang‐(1–7)–Mas in rats or in cultured fibroblasts and decreased the levels of collagen type I and α‐smooth muscle actin. Furthermore, exogenous Ang‐(1–7) had similar antifibrotic effects and increased the level of meprin α, a major Ac‐SDKP synthetase, both in vivo and in vitro. Compared with non‐silicotic patients exposed to silica, the level of serum ACE was increased in patients with silicosis phase III; the levels of Ang II and Ang‐(1–7) were high in patients with silicosis phase II; and the level of Ac‐SDKP was high in the silicosis phase III group. These data imply that Ac‐SDKP and Ang‐(1–7) have an interactive effect as regulatory peptides of the renin–angiotensin system and exert antifibrotic effects.

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Targeting the renin–angiotensin system as novel therapeutic strategy for pulmonary diseases

Cited by 159 publications

References 49 publications

Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19

Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19

COVID-19 and RAS: Unravelling an Unclear Relationship

Interaction of N‐acetyl‐seryl‐aspartyl‐lysyl‐proline with the angiotensin‐converting enzyme 2–angiotensin‐(1–7)–Mas axis attenuates pulmonary fibrosis in silicotic rats

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