Twenty years of progress in angiotensin converting enzyme 2 and its link to SARS-CoV-2 disease

2020 ◽  
Vol 134 (19) ◽  
pp. 2645-2664 ◽  
Author(s):  
Carlos M. Ferrario ◽  
Sarfaraz Ahmad ◽  
Leanne Groban
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Human Subjects ◽  
Adverse Outcomes ◽  
Converting Enzyme ◽  
Disease Evolution ◽  
Angiotensin Converting Enzyme 2 ◽  
High Affinity Binding Site ◽  
Receptor Blockers

Abstract The virulence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the aggressive nature of the disease has transformed the universal pace of research in the desperate attempt to seek effective therapies to halt the morbidity and mortality of this pandemic. The rapid sequencing of the SARS-CoV-2 virus facilitated identification of the receptor for angiotensin converting enzyme 2 (ACE2) as the high affinity binding site that allows virus endocytosis. Parallel evidence that coronavirus disease 2019 (COVID-19) disease evolution shows greater lethality in patients with antecedent cardiovascular disease, diabetes, or even obesity questioned the potential unfavorable contribution of angiotensin converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor blockers as facilitators of adverse outcomes due to the ability of these therapies to augment the transcription of Ace2 with consequent increase in protein formation and enzymatic activity. We review, here, the specific studies that support a role of these agents in altering the expression and activity of ACE2 and underscore that the robustness of the experimental data is associated with weak clinical long-term studies of the existence of a similar regulation of tissue or plasma ACE2 in human subjects.

scholarly journals Local Angiotensin-Converting Enzyme 2 Gene Expression in Kidney Allografts Is Not Affected by Renin-Angiotensin-Aldosterone Inhibitors

2021 ◽  
Vol 46 (2) ◽  
pp. 245-249
Author(s):  
Monika Cahova ◽  
Martin Kveton ◽  
Vojtech Petr ◽  
David Funda ◽  
Helena Dankova ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Kidney Transplant ◽  
Converting Enzyme ◽  
Transplant Recipients ◽  
Angiotensin Ii Receptor ◽  
Kidney Transplant Recipients ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Receptor Blockers

<b><i>Background:</i></b> Preclinical studies suggested that pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) by ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) may increase local angiotensin-converting enzyme 2 (<i>ACE2</i>) expression. <b><i>Methods:</i></b> In this study, we evaluated the effect of ACEi or ARB treatment on expression of <i>ACE2</i>, <i>ACE</i>, and <i>AGTR1</i> in 3-month protocol kidney allograft biopsies of stable patients using RT-qPCR (<i>n</i> = 48). Protein ACE2 expression was assessed using immunohistochemistry from paraffin sections. <b><i>Results:</i></b> The therapy with RAAS blockers was not associated with increased <i>ACE2, ACE</i>, or <i>ATGR1</i> expression in kidney allografts and also ACE2 protein immunohistochemistry did not reveal differences among groups. <b><i>Conclusions:</i></b> ACEis or ARBs in kidney transplant recipients do not affect local ACE2 expression. This observation supports long-term RAAS treatment in kidney transplant recipients, despite acute complications such as COVID-19 where ACE2 serves as the entry protein for infection.

scholarly journals Angiotensin Converting Enzyme 2 in COVID-19 infections and the implications of COVID-19 on major body systems

2020 ◽  
Vol 9 (2) ◽  
pp. 78-85
Author(s):  
Malyn M.L.K. Antoine ◽  
Yancheng Xu ◽  
Rimanatou Seyni-Boureima ◽  
Chrystal Deniza Antoine-Frank ◽  
Coumba Aicha Thiam ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Uncertain Information ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Modes Of Transmission ◽  
Novel Virus ◽  
And Control ◽  
The Relationship

COVID-19, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), was first identified in China in late 2019 and since then, this disease has become a pandemic affecting many countries across the globe. Due to this outbreak, many researchers have been diligently investigating this disease for the establishment of better methods of its treatment and control. Evidence from research has led to a plethora of valuable but uncertain information on the modes of transmission of COVID-19 and the mechanisms by which SARS-CoV-2 establishes infections in targeted tissues. It is now better understood that in this disease, SARS-CoV-2 gains entrance into cells by specifically binding ACE-2 (angiotensin-converting enzyme 2); ACE-2 serves as a potential receptor for the virus. The lungs, in addition to many other organs and tissues, express ACE-2 in varying degrees. Therefore, this review will examine the role of ACE-2 in COVID-19 and the secondary effects that COVID-19 has on organs that express ACE-2. To this end, it will assist in establishing the relationship between the ACE-2 receptor and SARS-CoV-2, bringing to the forefront the correlation between the symptomatology presentation, as well as the severity of infections experienced with COVID-19. Given this, it may even provide an avenue for the generation of treatment, or create a platform for the enhanced knowledge of this novel virus, and therefore, control, and maybe unravel the mystery for long term complications.  

scholarly journals Dysregulation of ACE (Angiotensin-Converting Enzyme)-2 and Renin-Angiotensin Peptides in SARS-CoV-2 Mediated Mortality and End-Organ Injuries

Hypertension ◽  
2021 ◽  
Author(s):  
Kaiming Wang ◽  
Mahmoud Gheblawi ◽  
Anish Nikhanj ◽  
Matt Munan ◽  
Erika MacIntyre ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Tumor Necrosis Factor Receptor ◽  
Renin Angiotensin System ◽  
Adverse Outcomes ◽  
Blood Collection ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Angiotensin Peptides

ACE (angiotensin-converting enzyme)-2 as the target for SARS-CoV-2 also negatively regulates the renin-angiotensin system. Pathological activation of ADAM17 (A disintegrin and metalloproteinase-17) may potentiate inflammation and diminish ACE2-mediated tissue protection through proteolytic shedding, contributing to SARS-CoV-2 pathogenesis. We aim to examine plasma soluble ACE2 and angiotensin profiles in relation to outcomes by enrolling consecutive patients admitted for COVID-19 with baseline blood collection at admission and repeated sampling at 7 days. The primary outcome was 90-day mortality, and secondary outcomes were the incidence of end-organ injuries. Overall, 242 patients were included, the median age was 63 (52–74) years, 155 (64.0%) were men, and 57 (23.6%) patients reached the primary end point. Baseline soluble ACE2 was elevated in COVID-19 but was not associated with disease severity or mortality. In contrast, an upward trajectory of soluble ACE2 at repeat sampling was independently associated with an elevated risk of mortality and incidence of acute myocardial injury and circulatory shock. Similarly, an increase in soluble tumor necrosis factor receptor levels was also associated with adverse outcomes. Plasma Ang I, Ang 1-7 (angiotensin 1–7) levels, and the Ang 1-7/Ang II (angiotensin II) ratio were elevated during SARS-CoV-2 infection related to downregulation of ACE activity at baseline. Moreover, patients having an upward trajectory of soluble ACE2 were characterized by an imbalance in the Ang 1-7/Ang II ratio. The observed dysregulation of ACE2 and angiotensin peptides with disease progression suggest a potential role of ADAM17 inhibition and enhancing the beneficial Ang 1-7/Mas axis to improve outcomes against SARS-CoV-2 infection.

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 Uremic Apelin and Leucocytic Angiotensin-Converting Enzyme 2 in CKD Patients

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 742
Author(s):  
Bogusz Trojanowicz ◽  
Christof Ulrich ◽  
Matthias Girndt
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Healthy Controls ◽  
Converting Enzyme ◽  
Blood Pressure Lowering ◽  
Angiotensin Converting Enzyme 2 ◽  
Pressure Lowering ◽  
The Impact ◽  
Progression Of Atherosclerosis

Apelin peptides (APLN) serve as second substrates for angiotensin-converting enzyme 2 (ACE2) and, in contrast to angiotensin II (AngII), exert blood-pressure lowering and vasodilatation effects through binding to G-coupled APLN receptor (APLNR). ACE2-mediated cleavage of the APLN may reduce its vasodilatory effects, but decreased ACE2 may potentiate the hypotensive properties of APLN. The role of APLN in uremia is unclear. We investigated the correlations between serum-APLN, leucocytic APLNR, and ACE2 in 32 healthy controls (NP), 66 HD, and 24 CKD3–5 patients, and the impact of APLN peptides on monocytic behavior and ACE2 expression under uremic conditions in vitro. We observed that serum APLN and leucocytic APLNR or SLCO2B1 were significantly elevated in uremic patients and correlated with decreased ACE2 on uremic leucocytes. APLN-treated THP-1 monocytes revealed significantly increased APLNR and ACE2, and reduced TNFa, IL-6, and MCSF. Uremic toxins induced a dramatic increase of miR-421 followed by significant reduction of ACE2 transcripts, partially counteracted with APLN-13 and -36. APLN-36 triggered the most potent transmigration and reduction of endothelial adhesion. These results suggest that although APLN peptides may partly protect against the decay of monocytic ACE2 transcripts, uremic milieu is the most dominant modulator of local ACE2, and likely to contribute to the progression of atherosclerosis.

P0527HYPERGLYCEMIA-ASSOCIATED ACUTE KIDNEY INJURY INCREASES THE SUSCEPTIBILITY TOWARDS NEUROLOGICAL DYSFUNCTION: ROLE OF ANGIOTENSIN II TYPE 2 RECEPTOR AND ANGIOTENSIN-CONVERTING ENZYME 2

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nisha Sharma ◽  
Anil Bhanudas Gaikwad
Keyword(s):  
Angiotensin Ii ◽  
Combination Therapy ◽  
Angiotensin Converting Enzyme ◽  
Neurological Dysfunction ◽  
Histopathological Analysis ◽  
Mrna Levels ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

Abstract Background and Aims In clinical settings, diabetics remain on higher risk of ischemic renal injury (IRI) than nondiabetic patients. In addition, IRI predisposes distant organs to dysfunction such as neurological impairments via activation of the pressor arm of renin-angiotensin system (RAS). In contrast, the role of depressor arm of RAS on IRI-associated neurological sequalae remains elusive. Hence, this study explored the role of angiotensin II type 2 receptor (AT2R) and angiotensin-converting enzyme 2 (ACE2) in IRI-associated neurological dysfunctions under nondiabetic (ND) and diabetes mellitus (DM) condition. Method Type 1 diabetes was induced by injecting streptozotocin (55 mg/kg i.p.). ND and DM rats with bilateral IRI were treated with AT2R agonist-Compound 21 (C21) (0.3 mg/kg/day, i.p.) or ACE2 activator-Diminazene Aceturate (Dize), (5 mg/kg/day, p.o.) per se or in combination therapy. Behavioural, biochemical, and histopathological analysis were done to assess IRI-induced neurological impairment. Moreover, immunohistochemistry, ELISA and qRT-PCR experiments were conducted for molecular mechanism analysis. Result In ND and DM rats, IRI caused hippocampal complications as evidenced by increased MDA and nitrite levels, augmented inflammatory cytokines (granulocyte colony stimulating factor, glial fibrillary acidic protein), altered protein and mRNA expressions of Ang II, Ang-(1-7), AT1R, AT2R and MasR. In contrast, concomitant therapy of C21 and Dize effectively normalised aforementioned hippocampal alterations. The protective effect of combination therapy was exerted due to augmented protein and mRNA levels of depressor arm components. Conclusion The current study demonstrated the protective role of AT2R agonist and ACE2 activator in IRI-associated neurological dysfunction through preventing oxidative stress, inflammation and upregulating brain depressor arm of RAS under ND and DM conditions.

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