Angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axis prevents pancreatic acinar cell inflammatory response via inhibition of the p38 mitogen-activated protein kinase/nuclear factor-κB pathway

Yu, Xinfeng; Cui, Lijian; Hou, Fei; Liu, Xiaoya; Wang, Yan; Wen, Yiping; Chi, Cheng; Li, Chunyun; Liu, Ruixia; Yin, Chenghong

doi:10.3892/ijmm.2017.3252

Cited by 36 publications

(34 citation statements)

References 54 publications

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“…Although Ang-(1-7) abolished the myostatin-induced NF-κB signaling activation, the mechanism has not been studied, and more analyses must be performed in order to elucidate it. In this line, the anti-NF-κB activity of Ang-(1-7) has been described in several tissues other than skeletal muscle as a counterregulatory effect to the Ang-II dependent NF-κB activation [50][51][52]. The relevance of the anti-atrophic effect of Ang-(1-7) and especially the depletion of NF-κB signaling has been discussed.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin (1-7) Decreases Myostatin-Induced NF-κB Signaling and Skeletal Muscle Atrophy

Aravena

Ábrigo

González

et al. 2020

IJMS

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Myostatin is a myokine that regulates muscle function and mass, producing muscle atrophy. Myostatin induces the degradation of myofibrillar proteins, such as myosin heavy chain or troponin. The main pathway that mediates protein degradation during muscle atrophy is the ubiquitin proteasome system, by increasing the expression of atrogin-1 and MuRF-1. In addition, myostatin activates the NF-κB signaling pathway. Renin-angiotensin system (RAS) also regulates muscle mass. Angiotensin (1-7) (Ang-(1-7)) has anti-atrophic properties in skeletal muscle. In this paper, we evaluated the effect of Ang-(1-7) on muscle atrophy and signaling induced by myostatin. The results show that Ang-(1-7) prevented the decrease of the myotube diameter and myofibrillar protein levels induced by myostatin. Ang-(1-7) also abolished the increase of myostatin-induced reactive oxygen species production, atrogin-1, MuRF-1, and TNF-α gene expressions and NF-κB signaling activation. Ang-(1-7) inhibited the activity mediated by myostatin through Mas receptor, as is demonstrated by the loss of all Ang-(1-7)-induced effects when the Mas receptor antagonist A779 was used. Our results show that the effects of Ang-(1-7) on the myostatin-dependent muscle atrophy and signaling are blocked by MK-2206, an inhibitor of Akt/PKB. Together, these data indicate that Ang-(1-7) inhibited muscle atrophy and signaling induced by myostatin through a mechanism dependent on Mas receptor and Akt/PKB.

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Section: Discussionmentioning

confidence: 99%

Angiotensin (1-7) Decreases Myostatin-Induced NF-κB Signaling and Skeletal Muscle Atrophy

Aravena

Ábrigo

González

et al. 2020

IJMS

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“…Ang-(1-7) reduces the expression of p38 MAPK and NF-κB and inflammatory factors such as IL-6, TNFα and IL-8 [48][49][50][51]. Thus, Ang-(1-7) per se has an anti-inflammatory effect and ameliorates inflammatory damages, as revealed in several animal studies [52,53].…”

Section: Ace2/masr Axismentioning

confidence: 91%

COVID-19 cytokine storm: The anger of inflammation

et al. 2020

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Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome.

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“…It is therefore imperative to determine whether this relationship is spurious in association or whether it is causative in nature or whether ACEI's have any effect on the viral acquisition and disease progress at all. ARDS is caused by the activation of angiotensin I, angiotensin II and AT1 receptor pathway, however stimulation of Mas receptor, MRGPR receptors , AT2 receptor and the ACE-2-angiotensin (1-7), pathways is found to be defensive as the [14,15] Mas receptor exerts an inhibitory effect on inflammation cellular growth and vascular mechanisms [16,17].…”

Section: Ace 2 Receptors In Covid-19mentioning

confidence: 99%

SARS-CoV-2: ACE inhibitors, disastrous or desirable?

Leclézio¹,

Robinson²,

Banerjee³

2020

J. Biomed. Sci.

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Background: The world has a current total of 6,663,304 confirmed cases of COVID-19 with a death count of 392,802 deaths according to the WHO (6 June 2020). Various risk factors for the acquisition and subsequent development of deadly complications due to the virus have been established. One such risk factor is the presence of cardiovascular disease, particularly hypertension as a comorbidity. It must be noted that JNC 8 advise the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers as first line drugs for the management of hypertension. ARDS is caused by the activation of angiotensin I, angiotensin II and AT1 receptor pathway, however stimulation of Mas receptor, MRGPR receptors, AT2 receptor and the ACE-2-angiotensin (1-7), pathways is found to be defensive. Mas receptor exerts an inhibitory effect on inflammation and cellular growth and vascular mechanisms. This research aims to examine the relationship between ACE inhibitors and the risk of COVID-19 infections with the goal of determining whether this relationship is spurious in association or whether it is causative in nature? More specifically, in this research article we will determine whether the SARS-CoV-2 virus has an affinity for ACE 2 receptors in humans. Furthermore, it will be determined whether ACE inhibitors would inhibit or facilitate an imminent COVID-19 infection in individuals as well as to determine whether patients currently using ACE inhibitors should continue or discontinue the drug therapy in order to minimize their susceptibility to acquiring COVID-19, and whether patients should start ACE inhibitor therapy if required during this pandemic. Conclusion: It is evident that ACE 2 receptors are the portal of entry for SARS-CoV-2. It is recommended that the use of RAAS inhibitors, viz ACE inhibitors and angiotensin receptor blockers is not stopped or decreased despite the ongoing pandemic as the results thereof may lead to the worsening of the patient’s comorbidity and may hasten death.

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Angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axis prevents pancreatic acinar cell inflammatory response via inhibition of the p38 mitogen-activated protein kinase/nuclear factor-κB pathway

Cited by 36 publications

References 54 publications

Angiotensin (1-7) Decreases Myostatin-Induced NF-κB Signaling and Skeletal Muscle Atrophy

Angiotensin (1-7) Decreases Myostatin-Induced NF-κB Signaling and Skeletal Muscle Atrophy

COVID-19 cytokine storm: The anger of inflammation

SARS-CoV-2: ACE inhibitors, disastrous or desirable?

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