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.

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.

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.

scholarly journals Angiotensin-Converting Enzyme 2 as a Possible Correlation between COVID-19 and Periodontal Disease

2020 ◽  
Vol 10 (18) ◽  
pp. 6224 ◽  
Author(s):  
Leonardo Mancini ◽  
Vincenzo Quinzi ◽  
Stefano Mummolo ◽  
Giuseppe Marzo ◽  
Enrico Marchetti
Keyword(s):  
Angiotensin Ii ◽  
Inflammatory Response ◽  
Angiotensin Converting Enzyme ◽  
Transforming Growth Factor ◽  
Tissue Injury ◽  
Interleukin 2 ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Cell Functions

SARS-CoV-2 propagation in the world has led to rapid growth and an acceleration in the discoveries and publications of various interests. The main focus of a consistent number of studies has been the role of angiotensin-converting enzyme 2 (ACE2) in binding the virus and its role in expression of the inflammatory response after transmission. ACE2 is an enzyme involved in the renin–angiotensin system (RAS), whose key role is to regulate and counter angiotensin-converting enzyme (ACE), reducing the amount of angiotensin II and increasing angiotensin 1–7 (Ang1–7), making it a promising drug target for treating cardiovascular diseases. The classical RAS axis, formed by ACE, angiotensin II (Ang II), and angiotensin receptor type 1 (AT1), activates several cell functions and molecular signalling pathways related to tissue injury and inflammation. In contrast, the RAS axis composed of ACE2, Ang1–7, and Mas receptor (MasR) exerts the opposite effect concerning the inflammatory response and tissue fibrosis. Recent studies have shown the presence of the RAS system in periodontal sites where osteoblasts, fibroblasts, and osteoclasts are involved in bone remodelling, suggesting that the role of ACE2 might have a fundamental function in the under- or overexpression of cytokines such as interleukin-6 (IL-6), interleukin-7 (IL-7), tumour necrosis factor alpha (TNF-α), interleukin-2 (IL-2), interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta (TGF-β), associated with a periodontal disorder, mainly during coinfection with SARS-CoV-2, where ACE2 is underexpressed and cannot form the ACE2–Ang1–7–MasR axis. This renders the patient unresponsive to an inflammatory process, facilitating periodontal loss.

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 Mica Can Alleviate TNBS-Induced Colitis in Mice by Reducing Angiotensin II and IL-17A and Increasing Angiotensin-Converting Enzyme 2, Angiotensin 1-7, and IL-10

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Mengdie Shen ◽  
Bibi Zhang ◽  
Mengyao Wang ◽  
Li’na Meng ◽  
Bin Lv
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Experimental Colitis ◽  
Control Group ◽  
Bloody Stool ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Trinitrobenzenesulfonic Acid ◽  
Angiotensin Converting Enzyme 2

Aim. To explore the treatment effect of mica on 2,4,6-trinitrobenzenesulfonic acid solution- (TNBS-) induced colitis in mice. Materials and Methods. Thirty male BALB/C mice were randomly divided into the control group, the TNBS group, and the mica group. Control mice were treated with saline solution. Experimental colitis was induced by TNBS (250 mg/kg/d) in the TNBS group and the mica group. After modeling, the mica group was treated with mica (180 mg/kg/d) for 3 days, while the TNBS group continued the treatment with TNBS. All solutions were injected intrarectally. During treatment, body weight and mice activity were monitored daily. After treatment, the colon tissues of mice were collected; angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), angiotensin 1-7 (Ang (1-7)), IL-17A, and IL-10 expression was analyzed by ELISA and immunohistochemistry. Results. Food intake, activity, and body weight gradually decreased in the TNBS group compared to the control group and the mica group (all P<0.05). Also, black stool adhesion in the anus and thin and bloody stool were observed in the TNBS group, but not in the other two groups. Moreover, the expression of Ang II, ACE2, Ang (1-7), IL-17A, and IL-10 in the TNBS group increased compared to that in the control group. Compared to the TNBS group, ACE2, Ang (1-7), and IL-10 in the mica group increased, while Ang II and IL-17A decreased (all P<0.05). Conclusion. Mica can alleviate TNBS-induced colitis in mice by regulating the inflammation process; it reduces Ang II and IL-17A and increases ACE2, IL-10, and Ang (1-7).

scholarly journals New Cardiovascular and Pulmonary Therapeutic Strategies Based on the Angiotensin-Converting Enzyme 2/Angiotensin-(1–7)/Mas Receptor Axis

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Anderson J. Ferreira ◽  
Tatiane M. Murça ◽  
Rodrigo A. Fraga-Silva ◽  
Carlos Henrique Castro ◽  
Mohan K. Raizada ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Therapeutic Strategies ◽  
Biologically Active ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
G Protein Coupled ◽  
Hydrolysis Of

Angiotensin (Ang)-(1–7) is now recognized as a biologically active component of the renin-angiotensin system (RAS). The discovery of the angiotensin-converting enzyme homologue ACE2 revealed important metabolic pathways involved in the Ang-(1–7) synthesis. This enzyme can form Ang-(1–7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1–9) with subsequent Ang-(1–7) formation. Additionally, it is well established that the G protein-coupled receptor Mas is a functional ligand site for Ang-(1–7). The axis formed by ACE2/Ang-(1–7)/Mas represents an endogenous counter regulatory pathway within the RAS whose actions are opposite to the vasoconstrictor/proliferative arm of the RAS constituted by ACE/Ang II/AT1receptor. In this review we will discuss recent findings concerning the biological role of the ACE2/Ang-(1–7)/Mas arm in the cardiovascular and pulmonary system. Also, we will highlight the initiatives to develop potential therapeutic strategies based on this axis.

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