LitCovid-sentences  

PMC:7556165 / 25680-30689 JSONTXT 17 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T164 0-42 Sentence denotes ACE2, the RAAS System and Cardioprotection
T165 43-307 Sentence denotes After the initial discovery of ACE2 in the heart and kidney, it is now clear that it is widely distributed in tissues (section Tissue Distribution of ACE2), where it exerts many physiological effects and may be involved in pathophysiological events (Turner, 2015).
T166 308-514 Sentence denotes The effect of ACE2 which has been more extensively investigated is the regulation of the RAAS system, where ACE2 counter-balances ACE, limiting the potent vasoconstrictive effect of angiotensin II (Ang-II).
T167 515-741 Sentence denotes The first evidence that ACE2 was involved in RAAS control came from the transgenic knockout mouse model (ACE2–/–), which was characterized by severe reduction of cardiac contractility and thinning of the left ventricular wall.
T168 742-873 Sentence denotes Interestingly, in this knockout model disruption of the ACE pathway could rescue the myocardial phenotype (Crackower et al., 2002).
T169 874-1009 Sentence denotes In another study, a selective ACE2 knockout model showed high blood pressure, worsened by the infusion of Ang-II (Gurley et al., 2006).
T170 1010-1148 Sentence denotes As a matter of fact, ACE2 displays its carboxypeptidase activity converting Ang-II to a heptapeptide, namely Ang1–7 (Turner et al., 2004).
T171 1149-1357 Sentence denotes ACE2 can also convert angiotensin I (Ang-I) to the non apeptide Ang1–9, which is in turn converted into Ang1–7 by ACE, competing with Ang-I and thus further decreasing Ang-II (Arendse et al., 2019; Figure 3).
T172 1358-1563 Sentence denotes Ang1–7 has been demonstrated to bind to the MasR receptor, which was initially regarded as an orphan receptor, since the use of a MasR antagonist caused inhibition of Ang1–7 effects (Alenina et al., 2008).
T173 1564-1797 Sentence denotes FIGURE 3 ACE2 signalling pathways: ACE2 displays its carboxypeptidase activity converting Ang-II (ANG II) to ANG1–7 and can also convert angiotensin I (ANG-I) to the nonapeptide Ang1–9, which is in turn converted into ANG1–7 by ACE.
T174 1798-1901 Sentence denotes ANG1-7 binds the MasR receptor to exert its effects on target organs (primarily heart, vessels, lungs).
T175 1902-2040 Sentence denotes ACE2 might also act via the bradykinin-DABK/BKB1R axis: the increased activity of the DABK axis triggers a proinflammatory cytokine storm.
T176 2041-2392 Sentence denotes In the last years the ACE2/Ang1–7/MasR system has been intensively studied: physiological effects on cardiomyocytes include modulation of Ca++ signaling and cytokine production, stimulation of cardiomyocytes progenitors and prevention of uncontrolled cell growth (Grobe et al., 2006; Flores-Muñoz et al., 2012; Souza et al., 2013; Chang et al., 2016).
T177 2393-2640 Sentence denotes Through the Ang1–7 pathway ACE2 produces endothelial antithrombotic effects, vasodilation, nitric oxide release, and inhibits vascular smooth muscle cells (VSMC) proliferation (Loot et al., 2002; Sampaio et al., 2007a,b; Fraga-Silva et al., 2008).
T178 2641-2828 Sentence denotes In preclinical studies Ang1–7 displayed antifibrotic effects, protecting from deleterious myocardial hypertrophy and modulating left ventricle remodeling after myocardial infarction (MI).
T179 2829-3163 Sentence denotes In animal models, Ang1–7 also showed an antiarrhythmic action (Ferreira et al., 2001; Santos et al., 2004; Grobe et al., 2006; Gomes et al., 2010), while compensatory ACE2 upregulation has been observed in explanted human hearts, in patients affected by ischemic or dilated cardiomyopathy (Goulter et al., 2004; Burrell et al., 2005).
T180 3164-3229 Sentence denotes Additional players contribute to ACE2-mediated cardio-protection.
T181 3230-3424 Sentence denotes Another substrate of ACE2 carboxypeptidase activity is Angiotensin A (Ang-A), identified in 2008, which has a similar, although less potent, vasopressor effect as AngII (Jankowski et al., 2007).
T182 3425-3568 Sentence denotes The product of the enzymatic reaction catalyzed by ACE2 is the peptide Ala-Ang (1–7) also known as alamandine (Lautner et al., 2013; Figure 3).
T183 3569-3704 Sentence denotes Alamandine receptor is a Mas-related G-protein coupled receptor, known as MrgD, which is expressed in cardiomyocytes and blood vessels.
T184 3705-3847 Sentence denotes MrgD knockout animals develop a severe cardiopathy and alamandine showed a cardioprotective effect in a model of sepsis (Santos et al., 2019).
T185 3848-4078 Sentence denotes Unlike ACE, ACE2 is not active on bradykinin, but it can degrade the active bradykinin metabolite des-Arg9 bradykinin (DABK), blocking the signaling pathway of the B1 bradykinin receptor (Vickers et al., 2002; Sodhi et al., 2018).
T186 4079-4186 Sentence denotes Other substrates of ACE2 include apelin-13/17, neurotensin, dynorphin A (1–13), and ghrelin (Turner, 2015).
T187 4187-4389 Sentence denotes Interestingly peptides of apelin family have been demonstrated to upregulate ACE2 expression in physiological condition and more actively during heart failure in in vivo experiments (Sato et al., 2013).
T188 4390-4654 Sentence denotes ACE2 in turn is able to regulate apelin bioavailability, establishing a negative feedback loop, and the crosstalk between RAAS, ACE2 and Apelin system might play a significant role in the pathophysiology of hypertension (Kalea and Batlle, 2010; Chen et al., 2015).
T189 4655-5009 Sentence denotes On the whole these findings suggest that ACE2 might exert antihypertensive and/or cardioprotective effects by different mechanisms, namely: (i) limiting the availability of ACE substrates, (ii) degrading Ang-II, (iii) activating the Ang1-7/MasR and/or Alamandine/MrgD pathways, (iv) interfering with other substrates, such as DABK and apelins (Figure 3).