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Article ; Online: Renin Angiotensin System Inhibition as treatment for Covid-19?

Williams, Professor Bryan

EClinicalMedicine

2021 Volume 37, Page(s) 101023

Language	English
Publishing date	2021-07-13
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2021.101023
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Article ; Online: Renin Angiotensin System Inhibition as treatment for Covid-19?

Professor Bryan Williams, FMedSci

EClinicalMedicine, Vol 37, Iss , Pp 101023- (2021)

2021

Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article: Nanoparticle approaches for the renin-angiotensin system.

Hettiarachchi, Sajini D / Kwon, Young M / Omidi, Yadollah / Speth, Robert C

Heliyon

2023 Volume 9, Issue 6, Page(s) e16951

Abstract: ... angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic ... The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders ... especially in hypertension, cardiovascular disease, and COVID-19. In this review article, we summarize ...

Abstract	The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor penetration across the blood-brain barrier, low bioavailability, and to some extent, short half-lives. Nanoparticle-mediated drug delivery systems (DDSs) are possible emerging alternatives to overcome such limitations. Nanoparticles are ideally 1-100 nm in size and are considered efficient DDSs mainly due to their unique characteristics, including water dispersity, prolonged half-life in blood circulation, smaller size, and biocompatibility. Nano-scale DDSs can reduce the drug dosage frequency and acute toxicity of drugs while enhancing therapeutic success. Different types of nanoparticles, such as chitosan, polymeric, and nanofibers, have been examined in RAS-related studies, especially in hypertension, cardiovascular disease, and COVID-19. In this review article, we summarize the physical and chemical characteristics of each nanoparticle to elaborate on their potential use in RAS-related nano-drug delivery research and clinical application.
Language	English
Publishing date	2023-06-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e16951
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Article ; Online: Nanoparticle approaches for the renin-angiotensin system

Sajini D. Hettiarachchi, PhD / Young M. Kwon / Yadollah Omidi / Robert C. Speth

Heliyon, Vol 9, Iss 6, Pp e16951- (2023)

2023

Abstract	The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor penetration across the blood-brain barrier, low bioavailability, and to some extent, short half-lives. Nanoparticle-mediated drug delivery systems (DDSs) are possible emerging alternatives to overcome such limitations. Nanoparticles are ideally 1–100 nm in size and are considered efficient DDSs mainly due to their unique characteristics, including water dispersity, prolonged half-life in blood circulation, smaller size, and biocompatibility. Nano-scale DDSs can reduce the drug dosage frequency and acute toxicity of drugs while enhancing therapeutic success. Different types of nanoparticles, such as chitosan, polymeric, and nanofibers, have been examined in RAS-related studies, especially in hypertension, cardiovascular disease, and COVID-19. In this review article, we summarize the physical and chemical characteristics of each nanoparticle to elaborate on their potential use in RAS-related nano-drug delivery research and clinical application.
Keywords	Renin-angiotensin system ; Nanoparticles ; Drug delivery ; Hypertension ; Cardiovascular disease ; COVID-19 ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Renin–Angiotensin System

Jaroslav Hrenak / Fedor Simko

International Journal of Molecular Sciences, Vol 21, Iss 8038, p

An Important Player in the Pathogenesis of Acute Respiratory Distress Syndrome

2020 Volume 8038

Abstract: ... acute lung injury can lead to pulmonary fibrosis. The renin–angiotensin system (RAS) plays a significant role ... 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. ...

Abstract	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-Arg 9 -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.
Keywords	ARDS ; renin–angiotensin system ; ACE2 ; COVID-19 ; SARS-CoV-2 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Impact of renin-angiotensin-aldosterone system inhibitors on COVID-19.

Matsuzawa, Yasushi / Kimura, Kazuo / Ogawa, Hisao / Tamura, Kouichi

Hypertension research : official journal of the Japanese Society of Hypertension

2022 Volume 45, Issue 7, Page(s) 1147–1153

Abstract: ... of renin-angiotensin system (RAS) inhibitors in COVID-19 have been debated as favorable, harmful, or neutral. Angiotensin ... Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the possible roles ... SARS-CoV-2) infection but also triggers a major mechanism of COVID-19 aggravation by promoting tissue ...

Abstract	Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the possible roles of renin-angiotensin system (RAS) inhibitors in COVID-19 have been debated as favorable, harmful, or neutral. Angiotensin-converting enzyme 2 (ACE2) not only is the entry route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but also triggers a major mechanism of COVID-19 aggravation by promoting tissue RAS dysregulation, which induces a hyperinflammatory state in several organs, leading to lung injury, hematological alterations, and immunological dysregulation. ACE inhibitors and angiotensin II type-1 receptor blockers (ARBs) inhibit the detrimental hyperactivation of the RAS by SARS-CoV-2 and increase the expression of ACE2, which is a counter-regulator of the RAS. Several studies have investigated the beneficial profile of RAS inhibitors in COVID-19; however, this finding remains unclear. Further prospective studies are warranted to confirm the role of RAS inhibitors in COVID-19. In this review, we summarize the potential effects of RAS inhibitors that have come to light thus far and review the impact of RAS inhibitors on COVID-19.
MeSH term(s)	Angiotensin Receptor Antagonists/pharmacology ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; COVID-19 ; Humans ; Peptidyl-Dipeptidase A/metabolism ; Renin-Angiotensin System ; SARS-CoV-2
Chemical Substances	Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-05-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1175297-x
ISSN	1348-4214 ; 0916-9636
ISSN (online)	1348-4214
ISSN	0916-9636
DOI	10.1038/s41440-022-00922-3
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Zs.A 3898: Show issues

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Article ; Online: Therapeutic Approaches in COVID-19 Patients: The Role of the Renin-Angiotensin System.

Ketabchi, Farzaneh / Jamzad, Sina

Canadian respiratory journal

2022 Volume 2022, Page(s) 8698825

Abstract: ... treatment strategies while emphasizing continuation of vaccination programs. The renin-angiotensin system ... administration of recombinant angiotensin-converting enzyme 2 has been proposed for the treatment of the disease ... in treating COVID-19 patients, but questions remain about which drugs will work and when. This review ...

Abstract	Two and a half years after COVID-19 was first reported in China, thousands of people are still dying from the disease every day around the world. The condition is forcing physicians to adopt new treatment strategies while emphasizing continuation of vaccination programs. The renin-angiotensin system plays an important role in the development and progression of COVID-19 patients. Nonetheless, administration of recombinant angiotensin-converting enzyme 2 has been proposed for the treatment of the disease. The catalytic activity of cellular ACE2 (cACE2) and soluble ACE2 (sACE2) prevents angiotensin II and Des-Arg-bradykinin from accumulating in the body. On the other hand, SARS-CoV-2 mainly enters cells via cACE2. Thus, inhibition of ACE2 can prevent viral entry and reduce viral replication in host cells. The benefits of bradykinin inhibitors (BKs) have been reported in some COVID-19 clinical trials. Furthermore, the effects of cyclooxygenase (COX) inhibitors on ACE2 cleavage and prevention of viral entry into host cells have been reported in COVID-19 patients. However, the administration of COX inhibitors can reduce innate immune responses and have the opposite effect. A few studies suggest benefits of low-dose radiation therapy (LDR) in treating acute respiratory distress syndrome in COVID-19 patients. Nonetheless, radiation therapy can stimulate inflammatory pathways, resulting in adverse effects on lung injury in these patients. Overall, progress is being made in treating COVID-19 patients, but questions remain about which drugs will work and when. This review summarizes studies on the effects of a recombinant ACE2, BK and COX inhibitor, and LDR in patients with COVID-19.
MeSH term(s)	Angiotensin II/metabolism ; Angiotensin II/pharmacology ; Angiotensin-Converting Enzyme 2 ; Bradykinin/metabolism ; Bradykinin/pharmacology ; Bradykinin/therapeutic use ; COVID-19 ; Humans ; Peptidyl-Dipeptidase A/metabolism ; Peptidyl-Dipeptidase A/therapeutic use ; Prostaglandin-Endoperoxide Synthases/metabolism ; Prostaglandin-Endoperoxide Synthases/pharmacology ; Renin-Angiotensin System/physiology ; SARS-CoV-2
Chemical Substances	Angiotensin II (11128-99-7) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Bradykinin (S8TIM42R2W)
Language	English
Publishing date	2022-09-26
Publishing country	Egypt
Document type	Journal Article ; Review
ZDB-ID	1213103-9
ISSN	1916-7245 ; 1198-2241
ISSN (online)	1916-7245
ISSN	1198-2241
DOI	10.1155/2022/8698825
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Zs.A 4140: Show issues

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Article: Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment.

Labandeira-Garcia, Jose L / Labandeira, Carmen M / Valenzuela, Rita / Pedrosa, Maria A / Quijano, Aloia / Rodriguez-Perez, Ana I

Biomedicines

2022 Volume 10, Issue 2

Abstract: ... of the tissue renin-angiotensin system (RAS) in the pathophysiology and severity of COVID-19 has been suggested ... The main link between RAS and COVID-19 is angiotensin-converting enzyme 2 (ACE2), a central RAS component ... A massive worldwide vaccination campaign constitutes the main tool against the COVID-19 pandemic ...

Abstract	A massive worldwide vaccination campaign constitutes the main tool against the COVID-19 pandemic. However, drug treatments are also necessary. Antivirals are the most frequently considered treatments. However, strategies targeting mechanisms involved in disease aggravation may also be effective. A major role of the tissue renin-angiotensin system (RAS) in the pathophysiology and severity of COVID-19 has been suggested. The main link between RAS and COVID-19 is angiotensin-converting enzyme 2 (ACE2), a central RAS component and the primary binding site for SARS-CoV-2 that facilitates the virus entry into host cells. An initial suggestion that the susceptibility to infection and disease severity may be enhanced by angiotensin type-1 receptor blockers (ARBs) and ACE inhibitors (ACEIs) because they increase ACE2 levels, led to the consideration of discontinuing treatments in thousands of patients. More recent experimental and clinical data indicate that ACEIs and, particularly, ARBs can be beneficial for COVID-19 outcome, both by reducing inflammatory responses and by triggering mechanisms (such as ADAM17 inhibition) counteracting viral entry. Strategies directly activating RAS anti-inflammatory components such as soluble ACE2, Angiotensin 1-7 analogues, and Mas or AT2 receptor agonists may also be beneficial. However, while ACEIs and ARBs are cheap and widely used, the second type of strategies are currently under study.
Language	English
Publishing date	2022-02-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10020502
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Article ; Online: What do we know about the renin angiotensin system and inflammatory bowel disease?

Lo, Sheng Wei / Segal, Jonathan P / Lubel, John S / Garg, Mayur

Expert opinion on therapeutic targets

2022 Volume 26, Issue 10, Page(s) 897–909

Abstract: Introduction: The renin-angiotensin system (RAS) is an important homeostatic pathway ... inhibition may have a role as anti-fibrotic adjunct therapy. Targeting the local gastrointestinal RAS ... in inflammatory bowel disease (IBD), and potential therapeutic implications.: Areas covered: An extensive online literature ...

Abstract	Introduction: The renin-angiotensin system (RAS) is an important homeostatic pathway, with emerging evidence for the impact of its components on inflammation and fibrosis in gastrointestinal tissues. This review aims to review current knowledge of the physiological mechanism of RAS in inflammatory bowel disease (IBD), and potential therapeutic implications. Areas covered: An extensive online literature review including Pubmed, Medline, and Google Scholar was undertaken. Discussion on the components of the RAS, localization, and physiological functions in the gastrointestinal tract, preclinical, and clinical data in IBD, and the relation with SARS-Cov-2 are covered in this review. Expert opinion: RAS inhibition may have a role as anti-fibrotic adjunct therapy. Targeting the local gastrointestinal RAS with novel modes of delivery may be a target for future therapeutics for IBD, given the widespread availability and safety of current options as utilized in other diseases. Further insight into the mechanism and downstream effects of gastrointestinal ACE2 may lead to a better understanding of the pathogenesis of IBD.
MeSH term(s)	Humans ; Renin-Angiotensin System ; SARS-CoV-2 ; COVID-19 ; Inflammatory Bowel Diseases/drug therapy ; Fibrosis
Language	English
Publishing date	2022-12-22
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2022.2157261
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Zs.A 5244: Show issues

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Article: Renin-angiotensin system inhibition in COVID-19 patients.

de Vries, A A F

Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation

2020 Volume 28, Issue 7-8, Page(s) 396–405

Abstract: ... of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there ... the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe. This has led ... to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19. In this point ...

Abstract	Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type‑1 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease. A number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2). ACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe. This has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19. In this point of view paper, possible scenarios regarding the impact of ACEI/ARB pharmacotherapy on COVID-19 are discussed in relation to the currently available evidence. Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV‑2 infections. Thus, unless contraindicated, use of ACEIs/ARBs in COVID-19 patients should be continued in line with the recent recommendations of medical societies.
Keywords	covid19
Language	English
Publishing date	2020-06-08
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2211468-3
ISSN	1876-6250 ; 1568-5888 ; 0929-7456
ISSN (online)	1876-6250
ISSN	1568-5888 ; 0929-7456
DOI	10.1007/s12471-020-01439-5
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