Role of renin-angiotensin system in liver diseases: an outline on the potential therapeutic points of intervention

Ahmadian, Elham; Pennefather, Peter; Eftekhari, Aziz; Heidari, Reza; Eghbal, Mohammad Ali

doi:10.1080/17474124.2016.1207523

Cited by 54 publications

(35 citation statements)

References 115 publications

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“…The most common liver diseases are hepatitis B and hepatitis C virus infections, alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD). Without proper treatment, all types of chronic hepatitis will progress into end-stage liver diseases, including cirrhosis, liver failure and hepatocellular carcinoma, which ultimately lead to death[20,24]. The pathological characteristics of chronic liver diseases include enhanced fibrosis, oxidative stress and inflammatory markers.…”

Section: Ras In Physiological and Pathophysiological Conditions Involmentioning

confidence: 99%

“…These processes are associated with sinusoidal capillarization and increased hepatic vascular resistance, eventually resulting in portal hypertension. Edema, ascites, hyperdynamic circulation and hepatorenal syndrome can occur because of compensatory mechanisms attempting to restore hepatic function[20]. The RAS is associated with all these processes.…”

Section: Ras In Physiological and Pathophysiological Conditions Involmentioning

confidence: 99%

“…The activation of the classical RAS arm, ACE-Ang II-AT 1 receptor, is one of the main factors responsible for renal vasoconstriction in HRS[16,20]. Plasma renin activity and Ang II levels are increased in HRS[79].…”

Section: Ras In Complications Of Liver Diseasesmentioning

confidence: 99%

“…Therefore, novel and alternative therapeutic approaches are needed to improve survival rate of HRS and to maintain patients in satisfactory clinical conditions for liver transplantation[77,94]. In this regard, evaluation of the role of molecules that modulate both RAS axes may be investigated in HRS[20]. …”

Section: Ras In Complications Of Liver Diseasesmentioning

confidence: 99%

“…It is well-established that RAS blockers, ACE inhibitors and angiotensin receptor antagonists (ARAs), can inhibit the ACE-Ang II-AT 1 arm, but also stimulate the activity of ACE2-Ang-(1-7)-Mas axis[15,17,18]. Both agents have been broadly used in the clinical practice for congestive heart failure, hypertension, chronic kidney disease[19] and seem to exert beneficial effects on liver diseases[20]. Table 1 displays the main opposite effects of both RAS axes.…”

Section: Introductionmentioning

confidence: 99%

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Renin angiotensin system in liver diseases: Friend or foe?

Silva

Rocha

et al. 2017

WJG

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In the last three decades, the understanding of the renin angiotensin system (RAS) has been changed by the discoveries of functional local systems, novel biologically active peptides, additional specific receptors, alternative pathways of angiotensin (Ang) II generation, and new roles for enzymes and precursor components other than those in Ang II synthesis. In this regard, the discovery that Ang-(1-7) opposes the pressor, proliferative, pro-fibrotic, and pro-inflammatory effects mediated by Ang II has contributed to the realization that the RAS is composed of two axes. The first axis consists of the angiotensin-converting enzyme (ACE), with Ang II as the end product, and the angiotensin type 1 (AT1) receptor as the main effector mediating the biological actions of Ang II. The second axis results from ACE2-mediated hydrolysis of Ang II, leading to the production of Ang-(1-7), with the Mas receptor as the main effector conveying the vasodilatory, anti-proliferative, anti-fibrotic, and anti-inflammatory effects of Ang-(1-7). Experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver diseases. In this manuscript, we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications, including hemodynamic changes and hepatorenal syndrome. The therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed.

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Section: Ras In Physiological and Pathophysiological Conditions Involmentioning

confidence: 99%

Section: Ras In Physiological and Pathophysiological Conditions Involmentioning

confidence: 99%

Section: Ras In Complications Of Liver Diseasesmentioning

confidence: 99%

Section: Ras In Complications Of Liver Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Renin angiotensin system in liver diseases: Friend or foe?

Silva

Rocha

et al. 2017

WJG

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Preparation and antagonistic effect of ACE inhibitory peptide from cashew

2019

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BACKGROUND Angiotensin‐converting enzyme (ACE) inhibitory peptides were found to alleviate acute hepatitis significantly. In this study, we purified and identified ACE inhibitory peptide from cashew to evaluate its protective role on alcohol‐induced acute hepatitis in mice. RESULTS The ACE inhibitory peptides were purified by using consecutive chromatographic techniques. One of these peptides (FETISFK) exhibited the highest ACE inhibition rate (91.04 ± 0.31%). In vivo, the results showed that ACE inhibitory peptide decreased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) caused by alcohol exposure. Moreover, it could increase the activities of superoxide dismutase (SOD) and glutathione (GSH), and decrease the level of malondialdehyde (MDA). It was also found to down‐regulate markedly the expression of interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α). It could also decrease the expression of ACE, angiotensin II (AngII) and angiotensin II type 1 receptor (AT1R). CONCLUSION These findings support the view that the ACE inhibitory peptide alleviated acute hepatitis by down‐regulating the ACE–AngII–AT1R axis, broadening the research approach to prevent acute hepatitis, and providing experimental data for the development and utilization of cashews. © 2019 Society of Chemical Industry

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Potential detrimental role of soluble ACE2 in severe COVID‐19 comorbid patients

Rahman

Hasan²,

Ahmed

2021

Reviews in Medical Virology

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Summary Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) enters the host cell by binding to angiotensin‐converting enzyme 2 (ACE2) receptor. Other important proteins involved in this process include disintegrin and metalloproteinase domain‐containing protein 17 (ADAM17) also known as tumour necrosis factor‐α‐converting enzyme and transmembrane serine protease 2. ACE2 converts angiotensin II (Ang II) to angiotensin (1–7), to balance the renin angiotensin system. Membrane‐bound ACE2 ectodomain shedding is mediated by ADAM17 upon viral spike binding, Ang II overproduction and in several diseases. The shed soluble ACE2 (sACE2) retains its catalytic activity, but its precise role in viral entry is still unclear. Therapeutic sACE2 is claimed to exert dual effects; reduction of excess Ang II and blocking viral entry by masking the spike protein. Nevertheless, the paradox is why SARS‐CoV‐2 comorbid patients struggle to attain such benefit in viral infection despite having a high amount of sACE2. In this review, we discuss the possible detrimental role of sACE2 and speculate on a series of events where protease primed or non‐primed virus–sACE2 complex might enter the host cell. As extracellular virus can bind many sACE2 molecules, sACE2 level could be reduced drastically upon endocytosis by the host cell. A consequential rapid rise in Ang II level could potentially aggravate disease severity through Ang II‐angiotensin II receptor type 1 (AT1R) axis in comorbid patients. Hence, monitoring sACE2 and Ang II level in coronavirus disease 2019 comorbid patients are crucial to ensure safe and efficient intervention using therapeutic sACE2 and vaccines.

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Role of renin-angiotensin system in liver diseases: an outline on the potential therapeutic points of intervention

Cited by 54 publications

References 115 publications

Renin angiotensin system in liver diseases: Friend or foe?

Renin angiotensin system in liver diseases: Friend or foe?

Preparation and antagonistic effect of ACE inhibitory peptide from cashew

Potential detrimental role of soluble ACE2 in severe COVID‐19 comorbid patients

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