scholarly journals ACE2 the Janus-faced protein – from cardiovascular protection to severe acute respiratory syndrome-coronavirus and COVID-19

2020 ◽  
Vol 134 (7) ◽  
pp. 747-750 ◽  
Author(s):  
Rhian M. Touyz ◽  
Hongliang Li ◽  
Christian Delles
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Basic Science ◽  
Physiological Role ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Multifunctional Protein ◽  
Angiotensin Converting Enzyme 2

Abstract Angiotensin converting enzyme 2 (ACE2) is the major enzyme responsible for conversion of Ang II into Ang-(1-7). It also acts as the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, which causes Coronavirus Disease (COVID)-19. In recognition of the importance of ACE2 and to celebrate 20 years since its discovery, the journal will publish a focused issue on the basic science and (patho)physiological role of this multifunctional protein.

scholarly journals Severe Acute Respiratory Syndrome-coronavirus 2 Infection: Role of Angiotensin-converting Enzyme 2

2020 ◽  
Vol 95 (4) ◽  
pp. 232-235
Author(s):  
Jinho Shin
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Human Studies ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Alveolar Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Human Lung Cells

A role of angiotensin-converting enzyme 2 (ACE2) in the coronavirus disease 2019 pandemic has been suggested, because it is the molecular receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2). ACE2 is known to provide a protective effect for cardiac and vascular tissues, because it generally counteracts angiotensin II (Ang II) activity. ACE2 downregulation has been implicated in the pathogenesis of cardiovascular disease. ACE inhibitors and angiotensin receptor blockers may enhance ACE2 mRNA expression and enzyme activity. However, this has not been demonstrated in lung tissue. In the lungs, Ang II induces vasoconstriction to prevent ventilation perfusion mismatch, while also increasing vascular permeability (which can precipitate pulmonary edema). ACE2 is expressed in 0.67% of human lung cells, 80% of which are type 2 alveolar cells. Men (of all ethnicities) and Asian individuals have been shown to express higher levels of ACE2 than women and non-Asian individuals, respectively. However, there are no data from human studies indicating that high ACE2 expression increases the likelihood of SARS-CoV2 infection. In animal studies, an increase in Ang II caused by SARS-CoV2 or spike protein interactions, in turn due to ACE2 downregulation, has been identified as the key mechanism underlying lung injury. In human studies of SARS-CoV2 infection, ACE2 overexpression was shown to cause inflammatory apoptosis and a cytokine storm. The actions of ACE2 and Ang II in SARS-CoV2-infected vascular and lung tissues differ between animals and humans. ACE2 expression levels pre- and post-SARS-CoV2 infection should be differentiated.

scholarly journals Do sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression explain increased severity and mortality of COVID-19 in males?

Diagnosis ◽  
2020 ◽  
Vol 7 (4) ◽  
pp. 385-386 ◽  
Author(s):  
Jens Vikse ◽  
Giuseppe Lippi ◽  
Brandon Michael Henry
Keyword(s):  
Mortality Rate ◽  
Severe Acute Respiratory Syndrome ◽  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Immunomodulatory Treatment ◽  
Angiotensin Converting Enzyme 2 ◽  
Cytopathic Effects ◽  
Severe Lung

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), shares similarities with the former SARS outbreak, which was caused by SARS-CoV-1. SARS was characterized by severe lung injury due to virus-induced cytopathic effects and dysregulated hyperinflammatory state. COVID-19 has a higher mortality rate in men both inside and outside China. In this opinion paper, we describe how sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression may explain the increased severity and mortality of COVID-19 in males. We highlight that immunomodulatory treatment must be tailored to the underlying immunobiology at different stages of disease. Moreover, by investigating sex-based immunobiological differences, we may enhance our understanding of COVID-19 pathophysiology and facilitate improved immunomodulatory strategies.

scholarly journals Gastrointestinal and kidney manifestations in SARS-CoV and SARS-CoV-2 infections: role of angiotensin-converting enzyme 2

2020 ◽  
Vol 25 (1) ◽  
pp. 7-20
Author(s):  
Fatemeh Maghool ◽  
◽  
Mohammad Hassan Emami ◽  
Samaneh Mohammadzadeh ◽  
Aida Heidari ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Gastrointestinal Symptoms ◽  
Renin Angiotensin System ◽  
Structural Similarity ◽  
Clinical Feature ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Kidney Impairment

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 2020, which has a substantial structural similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the outbreak in 2003, is currently a threat to global health. Lung involvement is the principal clinical feature in infected patients but extra-pulmonary clinical presentations are also common. The reasons for the extensive involvement of other organs are not yet clear. Angiotensin-converting enzyme 2 (ACE2), the key peptide of renin–angiotensin system (RAS), has recently identified as a major receptor for the both SARS-CoV and SARS-CoV-2 that might be a main target of coronavirus infection. ACE2 is mainly expressed in the pulmonary pneumocytes, the small intestine enterocytes as well as the proximal tubule epithelial cells of the kidneys. In addition to the respiratory tract infection symptoms, the noticeable prevalence of gastrointestinal symptoms as well as kidney impairment in hospitalized infected patients highlights other routes of infection/transmission. In present review, we discussed the role of RAS with emphasis on ACE2 in the pathogenesis of SARS-CoV and SARS-CoV-2, particularly in gastrointestinal and kidney manifestations of the diseases.

scholarly journals Angiotensin-Converting Enzyme 2 (ACE2) in the Pathogenesis of ARDS in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Keiji Kuba ◽  
Tomokazu Yamaguchi ◽  
Josef M. Penninger
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Neutralizing Antibodies ◽  
Cell Entry ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Angiotensin Converting Enzyme 2 ◽  
Infected People ◽  
Critical Attention ◽  
Novel Coronavirus

Seventeen years after the epidemic of SARS coronavirus, a novel coronavirus SARS-CoV-2-emerged resulting in an unprecedented pandemic. Angiotensin-converting enzyme 2 (ACE2) is an essential receptor for cell entry of SARS-CoV-2 as well as the SARS coronavirus. Despite many similarities to SARS coronavirus, SARS-CoV-2 exhibits a higher affinity to ACE2 and shows higher infectivity and transmissibility, resulting in explosive increase of infected people and COVID-19 patients. Emergence of the variants harboring mutations in the receptor-binding domain of the Spike protein has drawn critical attention to the interaction between ACE2 and Spike and the efficacies of vaccines and neutralizing antibodies. ACE2 is a carboxypeptidase which degrades angiotensin II, B1-bradykinin, or apelin, and thereby is a critical regulator of cardiovascular physiology and pathology. In addition, the enzymatic activity of ACE2 is protective against acute respiratory distress syndrome (ARDS) caused by viral and non-viral pneumonias, aspiration, or sepsis. Upon infection, both SARS-CoV-2 and SARS coronaviruses downregulates ACE2 expression, likely associated with the pathogenesis of ARDS. Thus, ACE2 is not only the SARS-CoV-2 receptor but might also play an important role in multiple aspects of COVID-19 pathogenesis and possibly post-COVID-19 syndromes. Soluble forms of recombinant ACE2 are currently utilized as a pan-variant decoy to neutralize SARS-CoV-2 and a supplementation of ACE2 carboxypeptidase activity. Here, we review the role of ACE2 in the pathology of ARDS in COVID-19 and the potential application of recombinant ACE2 protein for treating COVID-19.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor

2006 ◽  
Vol 81 (3) ◽  
pp. 1162-1173 ◽  
Author(s):  
Chien-Te K. Tseng ◽  
Cheng Huang ◽  
Patrick Newman ◽  
Nan Wang ◽  
Krishna Narayanan ◽  
...  
Keyword(s):  
Weight Loss ◽  
Severe Acute Respiratory Syndrome ◽  
Transgenic Mice ◽  
Angiotensin Converting Enzyme ◽  
Virus Replication ◽  
Clinical Manifestations ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Angiotensin Converting Enzyme 2 ◽  
Coronavirus Infection

ABSTRACT Animal models for severe acute respiratory syndrome (SARS) coronavirus infection of humans are needed to elucidate SARS pathogenesis and develop vaccines and antivirals. We developed transgenic mice expressing human angiotensin-converting enzyme 2, a functional receptor for the virus, under the regulation of a global promoter. A transgenic lineage, designated AC70, was among the best characterized against SARS coronavirus infection, showing weight loss and other clinical manifestations before reaching 100% mortality within 8 days after intranasal infection. High virus titers were detected in the lungs and brains of transgene-positive (Tg+) mice on days 1 and 3 after infection. Inflammatory mediators were also detected in these tissues, coinciding with high levels of virus replication. Lower virus titers were also detected in other tissues, including blood. In contrast, infected transgene-negative (Tg−) mice survived without showing any clinical illness. Pathologic examination suggests that the extensive involvement of the central nervous system likely contributed to the death of Tg+ mice, even though viral pneumonia was present. Preliminary studies with mice of a second lineage, AC63, in which the transgene expression was considerably less abundant than that in the AC70 line, revealed that virus replication was largely restricted to the lungs but not the brain. Importantly, despite significant weight loss, infected Tg+ AC63 mice eventually recovered from the illness without any mortality. The severity of the disease that developed in these transgenic mice—AC70 in particular—makes these mouse models valuable not only for evaluating the efficacy of antivirals and vaccines, but also for studying SARS coronavirus pathogenesis.

Primary role of angiotensin-converting enzyme-2 in cardiac production of angiotensin-(1–7) in transgenic Ren-2 hypertensive rats

2007 ◽  
Vol 292 (6) ◽  
pp. H3019-H3024 ◽  
Author(s):  
Aaron J. Trask ◽  
David B. Averill ◽  
Detlev Ganten ◽  
Mark C. Chappell ◽  
Carlos M. Ferrario
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Primary Role ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Direct Role ◽  
Compensatory Response ◽  
Angiotensin Converting Enzyme 2

Angiotensin-converting enzyme-2 (ACE2) converts angiotensin II (ANG II) to angiotensin-(1–7) [ANG-(1–7)], and this enzyme may serve as a key regulatory juncture in various tissues. Although the heart expresses ACE2, the extent that the enzyme participates in the cardiac processing of ANG II and ANG-(1–7) is equivocal. Therefore, we utilized the Langendorff preparation to characterize the ACE2 pathway in isolated hearts from male normotensive Sprague-Dawley [Tg(−)] and hypertensive [mRen2]27 [Tg(+)] rats. During a 60-min recirculation period with 10 nM ANG II, the presence of ANG-(1–7) was assessed in the cardiac effluent. ANG-(1–7) generation from ANG II was similar in both the normal and hypertensive hearts [Tg(−): 510 ± 55 pM, n = 20 vs. Tg(+): 497 ± 63 pM, n = 14] with peak levels occurring at 30 min after administration of the peptide. ACE2 inhibition (MLN-4760, 1 μM) significantly reduced ANG-(1–7) production by 83% (57 ± 19 pM, P < 0.01, n = 7) in the Tg(+) rats, whereas the inhibitor had no significant effect in the Tg(−) rats (285 ± 53 pM, P > 0.05, n = 10). ACE2 activity was found in the effluent of perfused Tg(−) and Tg(+) hearts, and it was highly associated with ACE2 protein expression ( r = 0.78). This study is the first demonstration for a direct role of ACE2 in the metabolism of cardiac ANG II in the hypertrophic heart of hypertensive rats. We conclude that predominant expression of cardiac ACE2 activity in the Tg(+) may be a compensatory response to the extensive cardiac remodeling in this strain.

scholarly journals A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury

2005 ◽  
Vol 11 (8) ◽  
pp. 875-879 ◽  
Author(s):  
Keiji Kuba ◽  
Yumiko Imai ◽  
Shuan Rao ◽  
Hong Gao ◽  
Feng Guo ◽  
...  
Keyword(s):  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Crucial Role ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Angiotensin Converting Enzyme 2

scholarly journals Bradykinin as a Probable Aspect in SARS-Cov-2 Scenarios: Is Bradykinin Sneaking out of our Sight?

2020 ◽  
Author(s):  
Seyed-Mohammad Ghahestani ◽  
Javad Mahmoudi ◽  
Sakineh Hajebrahimi ◽  
Amir-Babak Sioofy-Khojine ◽  
Hanieh Salehi-Pourmehr ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Disease Process ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
The World ◽  
Direct Target

The new virus SARS-CoV-2 is savagely spreading out over the world. The biologic studies show that the target receptor for the virus might be angiotensin-converting enzyme 2 (ACE2). This peptide is responsible for converting angiotensin II (Ang II), which is a profoundly active peptide, into Ang 1-7 with quite a balancing barbell function. It is emphasized that the direct target of the virus is ACE2 underlining the obvious difference with ACE. Nevertheless, we hypothesized that a back load build up effect on Ang II may usurp the ACE capacity and subsequently leave the bradykinin system unabated. We think there are clinical clues for dry cough and the presumed aggravating role of ACE inhibitors like captopril on the disease process. Thereby, we speculated that inhibition of bradykinin synthesis and/or blockade of bradykinin B2 receptor using Aprotinin/ecallantide and Icatibant, respectively, may hold therapeutic promise in severe cases and these molecules can be advanced to clinical trials.

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