Renin-angiotensin system and SARS-CoV-2 interaction: underlying mechanisms and potential clinical implications

Hrenak, Jaroslav; Zórad, Štefan; Šimko, Fedor

doi:10.4149/gpb_2020019

Cited by 4 publications

(6 citation statements)

References 6 publications

(8 reference statements)

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“…Moreover, the withdrawal of these drugs may induce a rebound phenomenon resulting in haemodynamic or atherosclerotic plaque instability. Additionally, in patients with cardiovascular pathologies and concomitant neurohumoral activation, there is virtually no adequate replacement therapy, especially in the severely ill population with saturated therapeutic schedule [13,14]. Thus, international societies of cardiology recommended maintaining the ACEI/ARB treatment of cardiovascular pathologies in patients with COVID-19 [14].…”

Section: Sars-cov-2 Ang II Ang 1-7 Interactionmentioning

confidence: 99%

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: potential allies in the COVID-19 pandemic instead of a threat?

Šimko

Baka

2021

Clinical Science

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Angiotensin-converting enzyme 2 (ACE2) is the leading player of the protective renin–angiotensin system (RAS) pathway but also the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAS inhibitors seemed to interfere with the ACE2 receptor, and their safety was addressed in COVID-19 patients. Pedrosa et al. (Clin. Sci. (Lond.) (2021), 135, 465–481) showed in rats that captopril and candesartan up-regulated ACE2 expression and the protective RAS pathway in lung tissue. In culture of pneumocytes, the captopril/candesartan-induced ACE2 up-regulation was associated with inhibition of ADAM17 activity, counterbalancing increased ACE2 expression, which was associated with reduced SARS-CoV-2 spike protein entry. If confirmed in humans, these results could become the pathophysiological background for justifying RAS inhibitors as cornerstone cardiovascular protectives even during COVID-19 pandemic.

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Section: Sars-cov-2 Ang II Ang 1-7 Interactionmentioning

confidence: 99%

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: potential allies in the COVID-19 pandemic instead of a threat?

Šimko

Baka

2021

Clinical Science

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“…Several theories aiming to explain the effect of RAS inhibiting treatment on SARS-CoV-2 infection at cellular and/or subcellular levels have been proposed [25,86,87]. However, the physiological and pathological roles of the majority of the involved molecules remain only partly understood and the complexity of their interactions raises a number of questions requiring further investigation.…”

Section: Aceis and Arbs In Covid-19mentioning

confidence: 99%

“…However, this treatment could presumably also suppress Ang II conversion to Ang 1-7 by ACE2 and enhance the activity of the pro-inflammatory RAS axis. On the other hand, it has been suggested that treatment with a putatively competitive ACE2 agonist with higher receptor affinity compared to SARS-CoV or SARS-CoV-2 might block the internalization of the virus and stimulate ACE2/Ang 1-7-mediated signaling [25]. In addition, it seems logical to suppose that the stimulation of the ACE2/Ang 1-7 axis, e.g., by Ang 1-7, rhACE2 or ACE2 agonists in co-treatment with established agents inhibiting ACE or AT1R, could offer additional protection compared to monotherapy.…”

Section: Perspectives For Drug Developmentmentioning

confidence: 99%

“…The other, involving ACE2, Ang 1-7 and the Mas receptor (MasR), mediates the vasodilatory, anti-inflammatory and anti-fibrotic actions of the RAS. However, the interactions of the RAS family members are multidirectional, involving a bulk of molecules whose physiological role has yet to be elucidated [8,11,25]. In addition, the RAS is closely related to the kinin-kalikrein system, regulating vascular tone and permeability, since ACE and ACE2 participate in the inactivation of bradykinin and des-Arg 9 -bradykinin (DABK), respectively [26,27].…”

Section: Introductionmentioning

confidence: 99%

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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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“… 1 , 2 SARS-COV-2 reaches the liver through the high number of Angiotensin Converting Enzyme-2 (ACE2) receptors on the hepatic bile duct cell surface and may cause abnormalities in liver function tests. 3 - 5 There are also publications showing that viruses that affect the respiratory system can also damage liver cells through the CD8+ mediated immune response. 6 …”

Section: Introductionmentioning

confidence: 99%

Comparison of cases with and without acute liver injury in pregnant women with SARS-CoV-2 infection; obstetric and neonatal outcomes

Kulhan,

Orgul,

Avci

et al. 2023

Pak J Med Sci

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Background and objective: The effect of SARS-CoV-2 infection on the liver during pregnancy and the impact of SARS-COV-2-related liver injury during pregnancy on obstetric and neonatal outcomes are not yet clear. The aim of this study was to determine the clinical features of pregnant women at risk of liver injury and to investigate the effect of liver dysfunction on obstetric and perinatal outcomes. Methodology: Pregnant women who were followed up and treated at Selcuk University Medical Faculty Hospital and diagnosed with COVID-19 were determined retrospectively. All pregnant women whose PCR test results were positive between March 1, 2020 and July 31, 2022 were included. A total of 96 PCR positive pregnant women were included in the study. The patients were divided into two groups as those with and without liver damage. Both groups were compared in terms of obstetric and neonatal outcomes. Results: While liver damage findings were observed in 34.4% of the 96 pregnant included in the study; No liver damage was observed in 65.6% of the patients. White blood cell, neutrophil, ferritin, D-dimer, troponin, C-reactive protein, systemic immune-inflammation index, interleukin-6, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase levels were higher in patients with liver injury compared to pregnant women without liver injury. Prematurity, premature rupture of membranes, preterm premature rupture of membranes, preeclampsia and fetal death were observed relatively more in the patient group with liver injury, there was no statistical significiant difference between the groups in terms of these complications. Unfortunately, maternal death occurred in four mothers with liver injury and in one patient without liver injury. Birthweight, APGAR scores and obstetric complication rates were similar between two groups. Conclusion: Our study showed that pregnant patients with liver damage had worse inflammatory response than those without liver damage. Women with elevated liver enzymes tend to have severe disease, but obstetric and perinatal outcomes were similar between groups with and without liver damage. doi: https://doi.org/10.12669/pjms.40.3.7746 How to cite this: Kulhan NG, Orgul G, Avci F, Kulhan M. Comparison of cases with and without acute liver injury in pregnant women with SARS-CoV-2 infection; obstetric and neonatal outcomes. Pak J Med Sci. 2024;40(3):---------. doi: https://doi.org/10.12669/pjms.40.3.7746 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Renin-angiotensin system and SARS-CoV-2 interaction: underlying mechanisms and potential clinical implications

Cited by 4 publications

References 6 publications

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: potential allies in the COVID-19 pandemic instead of a threat?

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: potential allies in the COVID-19 pandemic instead of a threat?

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

Comparison of cases with and without acute liver injury in pregnant women with SARS-CoV-2 infection; obstetric and neonatal outcomes

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