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Article: Angiotensin-converting enzyme 2 expression is not induced by the renin-angiotensin system in the lung.

Baba, Ryuta / Oki, Kenji / Itcho, Kiyotaka / Kobuke, Kazuhiro / Nagano, Gaku / Ohno, Haruya / Yoneda, Masayasu / Hattori, Noboru

ERJ open research

2020 Volume 6, Issue 4

Abstract: ... of severe acute respiratory syndrome coronavirus 2, is not regulated by angiotensin II or renin-angiotensin system inhibitors #COVID19 ... Pulmonary expression of angiotensin-converting enzyme 2, which is a receptor ...

Abstract	Pulmonary expression of angiotensin-converting enzyme 2, which is a receptor of severe acute respiratory syndrome coronavirus 2, is not regulated by angiotensin II or renin-angiotensin system inhibitors #COVID19
Keywords	covid19
Language	English
Publishing date	2020-10-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2827830-6
ISSN	2312-0541
ISSN	2312-0541
DOI	10.1183/23120541.00402-2020
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Angiotensin-converting enzyme 2 expression is not induced by the renin–angiotensin system in the lung

Ryuta Baba / Kenji Oki / Kiyotaka Itcho / Kazuhiro Kobuke / Gaku Nagano / Haruya Ohno / Masayasu Yoneda / Noboru Hattori

ERJ Open Research, Vol 6, Iss

2020 Volume 4

Keywords	Medicine ; R
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Angiotensin-converting enzyme 2 expression is not induced by the renin-angiotensin system in the lung

Baba, R. / Oki, K. / Itcho, K. / Kobuke, K. / Nagano, G. / Ohno, H. / Yoneda, M. / Hattori, N.

ERJ Open Res

Abstract	Pulmonary expression of angiotensin-converting enzyme 2, which is a receptor of severe acute respiratory syndrome coronavirus 2, is not regulated by angiotensin II or renin-angiotensin system inhibitors #COVID19 https://bit ly/3fkopuO
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #843021
Database	COVID19

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Article ; Online: Overexpression of angiotensin-converting enzyme 2 by renin-angiotensin system inhibitors. Truth or myth? A systematic review of animal studies.

Kai, Hisashi / Kai, Mamiko / Niiyama, Hiroshi / Okina, Norihito / Sasaki, Motoki / Maeda, Takanobu / Katoh, Atsushi

Hypertension research : official journal of the Japanese Society of Hypertension

2021 Volume 44, Issue 8, Page(s) 955–968

Abstract: ... cardiovascular diseases by counter regulating the renin-angiotensin system (RAS). ACE2 is also the receptor ... Angiotensin-converting enzyme 2 (ACE2) protects against organ damage in hypertension and ... than half the control level (repression) in 28 models (40 experiments). In 72 experiments, RASIs did not ...

Abstract	Angiotensin-converting enzyme 2 (ACE2) protects against organ damage in hypertension and cardiovascular diseases by counter regulating the renin-angiotensin system (RAS). ACE2 is also the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on the claim that RAS inhibitors (RASIs) cause ACE2 overexpression in some animal experiments, concerns have arisen that RASIs may aggravate SARS-CoV-2 infection and coronavirus disease-2019 severity in RASI-treated patients. To achieve a comprehensive review, a systematic search of MEDLINE/PubMed was conducted regarding the effects of RASIs on tissue ACE2 mRNA/protein expression in healthy animals and animal models of human diseases. We identified 88 eligible articles involving 168 experiments in the heart, kidneys, lungs, and other organs. Three of 38 experiments involving healthy animals showed ACE2 expression greater than twice that of the control (overexpression). Among 102 disease models (130 experiments), baseline ACE2 was overexpressed in 16 models (18 experiments) and less than half the control level (repression) in 28 models (40 experiments). In 72 experiments, RASIs did not change ACE2 levels from the baseline levels of disease models. RASIs caused ACE2 overexpression compared to control levels in seven experiments, some of which were unsupported by other experiments under similar conditions. In 36 experiments, RASIs reversed or prevented disease-induced ACE2 repression, yielding no or marginal changes. Therefore, ACE2 overexpression appears to be a rare rather than common consequence of RASI treatment in healthy animals and disease models. Future studies should clarify the pathophysiological significance of RASI-induced reversal or prevention of ACE2 repression in disease models.
MeSH term(s)	Angiotensin-Converting Enzyme 2/metabolism ; Angiotensin-Converting Enzyme Inhibitors/adverse effects ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Animals ; Antihypertensive Agents/adverse effects ; Antihypertensive Agents/pharmacology ; COVID-19 ; Disease Models, Animal ; Gene Expression/drug effects ; MEDLINE ; Renin-Angiotensin System/drug effects
Chemical Substances	Angiotensin-Converting Enzyme Inhibitors ; Antihypertensive Agents ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-03-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	1175297-x
ISSN	1348-4214 ; 0916-9636
ISSN (online)	1348-4214
ISSN	0916-9636
DOI	10.1038/s41440-021-00641-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 3898: Show issues

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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: ... converting enzyme 2 (ACE2) not only is the entry route of severe acute respiratory syndrome coronavirus 2 ... of renin-angiotensin system (RAS) inhibitors in COVID-19 have been debated as favorable, harmful, or neutral. Angiotensin ... the expression of ACE2, which is a counter-regulator of the RAS. Several studies have investigated the beneficial ...

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
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 3898: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Focus on clinical practice: angiotensin-converting enzyme 2 and corona virus disease 2019: pathophysiology and clinical implications.

Barillà, Francesco / Bassareo, Pier Paolo / Calcaterra, Giuseppe / Romeo, Francesco / Mehta, Jawahar L

Journal of cardiovascular medicine (Hagerstown, Md.)

2020 Volume 21, Issue 9, Page(s) 630–633

Abstract: ... but whether an increase in ACE2 activity could facilitate the infection is not yet demonstrated. However, this aspect has ... between the spike protein of COVID-19 and the enzyme is crucial for the virus to enter the target cells ... activity and induce injury to the lungs or cardiovascular system. ...

Abstract	: ACE2 receptor has a broad expression pattern in the cellular membrane and provides a protective action against the development of cardiovascular diseases. Recently, this enzyme has become of extreme interest during the pandemic infection of COVID-19 (coronavirus disease 2019). This virus invades alveolar epithelium and cardiomyocytes using ACE2 as a transmembrane receptor. ACE2 is a counter-regulatory peptide that degrades Ang II into Ang 1-7, thereby attenuating the biological effects of the AT1 receptor. The binding between the spike protein of COVID-19 and the enzyme is crucial for the virus to enter the target cells, but whether an increase in ACE2 activity could facilitate the infection is not yet demonstrated. However, this aspect has raised many concerns about the use of ACE inhibitors or ARBs in infected patients or patients at risk of infection. It appears that cellular infection leads to a reduction in ACE2 expression and an increase in the activity of the Ang II--AT1 axis, which leads to the release of pro-inflammatory cytokines, ARDS, myocarditis, and hypercoagulability with the possibility of exacerbation of acute coronary syndrome, induction of pulmonary embolism, or appearance of disseminated intravascular coagulation. Therefore, ACE inhibitors or angiotensin receptor blocker drugs should be continued in infected patients, as their discontinuation can increase Ang II activity and induce injury to the lungs or cardiovascular system.
MeSH term(s)	Angiotensin Receptor Antagonists/pharmacology ; Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Betacoronavirus/physiology ; COVID-19 ; Cardiovascular Diseases/complications ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/metabolism ; Coronavirus Infections/metabolism ; Coronavirus Infections/virology ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/virology ; Renin-Angiotensin System/drug effects ; Renin-Angiotensin System/physiology ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Internalization
Chemical Substances	Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-07-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2223461-5
ISSN	1558-2035 ; 1558-2027
ISSN (online)	1558-2035
ISSN	1558-2027
DOI	10.2459/JCM.0000000000001071
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 5210: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Role and mechanism of angiotensin-converting enzyme 2 in acute lung injury in coronavirus disease 2019.

Liu, Meng-Yuan / Zheng, Bo / Zhang, Yan / Li, Jian-Ping

Chronic diseases and translational medicine

2020 Volume 6, Issue 2, Page(s) 98–105

Abstract: ... not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified ... the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1-7, which exerts a beneficial effect ... we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying ...

Abstract	Coronavirus disease 2019 is a major threat to public health globally. Though its pathogenesis has not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the cell. Here, we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism. As a receptor for coronavirus, ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus (SARS-CoV). The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans. On the other hand, ACE2 negatively regulates the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1-7, which exerts a beneficial effect on coronavirus-induced acute lung injury. Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection. The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor (ACEI) or angiotensin Ⅱ type 1 receptor blocker (ARB). To date, no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2, and hence, it is not advisable to discontinue such drugs in patients with cardiovascular disease.
Keywords	covid19
Language	English
Publishing date	2020-05-19
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2831148-6
ISSN	2589-0514 ; 2589-0514
ISSN (online)	2589-0514
ISSN	2589-0514
DOI	10.1016/j.cdtm.2020.05.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Role and mechanism of angiotensin-converting enzyme 2 in acute lung injury in coronavirus disease 2019

Meng-Yuan Liu / Bo Zheng / Yan Zhang / Jian-Ping Li

Chronic Diseases and Translational Medicine, Vol 6, Iss 2, Pp 98-

2020 Volume 105

Abstract: ... not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified ... the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1–7, which exerts a beneficial effect ... we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying ...

Abstract	Coronavirus disease 2019 is a major threat to public health globally. Though its pathogenesis has not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the cell. Here, we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism. As a receptor for coronavirus, ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus (SARS-CoV). The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans. On the other hand, ACE2 negatively regulates the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1–7, which exerts a beneficial effect on coronavirus-induced acute lung injury. Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection. The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor (ACEI) or angiotensin Ⅱ type 1 receptor blocker (ARB). To date, no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2, and hence, it is not advisable to discontinue such drugs in patients with cardiovascular disease.
Keywords	Severe acute respiratory syndrome coronavirus 2 ; Angiotensin-converting enzyme 2 ; Acute lung injury ; Medicine (General) ; R5-920 ; covid19
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	KeAi Communications Co., Ltd.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Role and mechanism of angiotensin-converting enzyme 2 in acute lung injury in coronavirus disease 2019

Liu, Meng-Yuan / Zheng, Bo / Zhang, Yan / Li, Jian-Ping

Chronic Dis. Transl. Med.

Abstract: ... not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified ... the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1–7, which exerts a beneficial effect ... we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying ...

Abstract	Coronavirus disease 2019 is a major threat to public health globally. Though its pathogenesis has not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the cell. Here, we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism. As a receptor for coronavirus, ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus (SARS-CoV). The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans. On the other hand, ACE2 negatively regulates the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1–7, which exerts a beneficial effect on coronavirus-induced acute lung injury. Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection. The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor (ACEI) or angiotensin Ⅱ type 1 receptor blocker (ARB). To date, no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2, and hence, it is not advisable to discontinue such drugs in patients with cardiovascular disease.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #306057
Database	COVID19

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Article ; Online: Midkine regulation of the renin-angiotensin system.

Kadomatsu, Kenji

Current hypertension reports

2010 Volume 12, Issue 2, Page(s) 74–79

Abstract: ... its significance in the renin-angiotensin system and the kidney-lung interaction. ... involves the renin-angiotensin system. We have recently reported that the growth factor midkine is a novel ... regulator of the renin-angiotensin system. Midkine is a heparin-binding growth factor so far implicated ...

Abstract	Hypertension and chronic kidney disease are often associated. The pathogenesis of these diseases involves the renin-angiotensin system. We have recently reported that the growth factor midkine is a novel regulator of the renin-angiotensin system. Midkine is a heparin-binding growth factor so far implicated in neuronal differentiation, neuroprotection, cardioprotection, inflammation, and cancer development. In a mouse model of chronic kidney disease induced by 5/6 nephrectomy, midkine is produced in the lung and in turn upregulates angiotensin-converting enzyme expression. Hypertension associated with 5/6 nephrectomy is not observed in midkine-deficient mice. Conversely, supplemental administration of midkine to the deficient mice induces hypertension. This review describes the molecular characteristics of midkine and its significance in the renin-angiotensin system and the kidney-lung interaction.
MeSH term(s)	Acetylcholinesterase/biosynthesis ; Acute Kidney Injury ; Aldosterone ; Angiotensin II ; Animals ; Central Nervous System ; Cytokines/physiology ; Fibroblast Growth Factors ; Humans ; Hypertension/pathology ; Inflammation/pathology ; Kidney Failure, Chronic/pathology ; Lung ; Mice ; Midkine ; Receptors, Fibroblast Growth Factor ; Renin ; Renin-Angiotensin System/physiology ; Risk Factors
Chemical Substances	Cytokines ; Receptors, Fibroblast Growth Factor ; Angiotensin II (11128-99-7) ; Midkine (137497-38-2) ; Aldosterone (4964P6T9RB) ; Fibroblast Growth Factors (62031-54-3) ; Acetylcholinesterase (EC 3.1.1.7) ; Renin (EC 3.4.23.15)
Language	English
Publishing date	2010-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-010-0092-8
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