Epistemic_Statements  

CORD-19:f22ac602926d152936dd6af839da45bf8290e038 JSONTXT 8 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 574-789 Epistemic_statement denotes As the catalytic efficiency of ACE2 is approximately 400-fold higher with Ang II as a substrate than with Ang I, this axis is possibly acting as a counter-regulatory system against the ACE/Ang II/AT 1 receptor axis.
T2 790-887 Epistemic_statement denotes The signaling pathway of the ACE2-Ang-(1-7) axis has not yet been totally and clearly understood.
T3 888-977 Epistemic_statement denotes However, a recent report suggests that the Mas oncogene acts as a receptor for Ang-(1-7).
T4 978-1031 Epistemic_statement denotes Intracellular signaling through Mas is not clear yet.
T5 1032-1205 Epistemic_statement denotes Several factors such as Akt phosphorylation, protein kinase C activation and mitogen-activated protein (MAP) kinase inhibition seem to be involved in this signaling pathway.
T6 1206-1312 Epistemic_statement denotes Further investigations are needed to clarify the regulation and mechanism of action of ACE2 and Ang-(1-7).
T7 1313-1458 Epistemic_statement denotes However, this second axis through ACE2 and Ang-(1-7) in RAS can be an important target for the therapy of cardiovascular and metabolic disorders.
T8 1460-1544 Epistemic_statement denotes The renin-angiotensin system (RAS) has a critical role in the cardiovascular system.
T9 2120-2254 Epistemic_statement denotes 3 In cardiovascular diseases, AT 2 -receptor stimulation seems to antagonize the signaling associated with AT 1 -receptor stimulation.
T10 2482-2664 Epistemic_statement denotes 4 In this context, AT 2 -receptor agonists, such as compound 21, have been newly developed and are expected to function as useful agents against pathological disorders in the future.
T11 2665-2716 Epistemic_statement denotes 5 Recently, a new axis of RAS has been established.
T12 2806-2902 Epistemic_statement denotes 6, 7 The mechanisms of action of Ang-(1-7) are still being investigated by many research groups.
T13 3409-3513 Epistemic_statement denotes 4 Recent studies indicate that Ang II is also involved in the onset of diabetes and metabolic disorders.
T14 3586-3656 Epistemic_statement denotes This classical axis can be called as the ACE-AngII-AT 1 receptor axis.
T15 3657-3763 Epistemic_statement denotes Such findings are closely related to the development of RAS inhibitors, such as the ACE inhibitor and ARB.
T16 4797-4847 Epistemic_statement denotes However, these efforts produced the ACE inhibitor.
T17 5857-5942 Epistemic_statement denotes AT 1 -receptor stimulation seems to activate the EGF receptor in the plasma membrane.
T18 6439-6733 Epistemic_statement denotes [13] [14] [15] ROLES OF ACE2, ANG-(1-7) AND THE MAS AXIS-A NEW RAS PATHWAY Possible effects such as vasodilation mediated by Ang-(1-7) have been reported; however, the mechanisms leading to Ang-(1-7) production and its receptor were unclear, resulting in the delay of Ang-(1-7)based researches.
T19 6993-7133 Epistemic_statement denotes 18 As Ang-(1-9) can be converted to Ang-(1-7) by ACE or by other peptidases, ACE2 facilitates Ang-(1-7) production by two separate pathways.
T20 7186-7306 Epistemic_statement denotes It might be possible that Ang-(1-7) is a degradation product of Ang II and one of the inactivation mechanisms of Ang II.
T21 7307-7384 Epistemic_statement denotes However, recent studies indicate that Ang-(1-7) has more active roles in RAS.
T22 7488-7566 Epistemic_statement denotes This effect seemed to be mediated by the bradykinin-NO (nitric oxide) pathway.
T23 7567-7925 Epistemic_statement denotes 18, 20 Accordingly, these results suggest that Ang-(1-7) antagonized the pressor effect of AT 1 -receptor stimulation, suggesting that it may act as a kind of AT 1 -receptor antagonist, thereby resulting in a blood-pressure-lowering effect and an organ-protective effect, such as a reduction of cardiac hypertrophy and fibrosis and renal damage ( Figure 3 ).
T24 8663-8902 Epistemic_statement denotes 26, 27 It has been discovered that the catalytic efficiency of ACE2 is approximately 400-fold higher with Ang II as a substrate than with Ang I, 17 suggesting that this second arm of the system acts as a counter-regulator of the first arm.
T25 8903-9038 Epistemic_statement denotes Previous reports suggest that olmesartan, an ARB, increased the plasma concentration of Ang-(1-7) and the cardiac ACE2expression level.
T26 9039-9222 Epistemic_statement denotes 28, 29 Another ARB, losartan, also induced similar changes; however, its dose was 100-fold higher than that of olmesartan, 28 suggesting that this effect of ARB is not a class effect.
T27 9223-9361 Epistemic_statement denotes A more detailed analysis could show the regulation of ACE2 and Mas, which could contribute toward a new drug discovery for regulating RAS.
T28 9362-9552 Epistemic_statement denotes Recent studies on the function of ACE2 suggest that ACE2 has an important role in the severity of lung failure, such as in acute respiratory distress syndrome (ARDS) or in acute lung injury.
T29 9553-9784 Epistemic_statement denotes 30 Moreover, it has been shown that the severe acute respiratory syndrome (SARS) corona virus utilizes ACE2 as an essential receptor for cell fusion and for in vivo infections, suggesting that ACE2 contributes to SARS pathogenesis.
T30 9785-9940 Epistemic_statement denotes 31 These results indicate that ACE2 activity has an important role not only in cardiovascular diseases but also in damages or dysfunctions of other organs.
T31 9941-10070 Epistemic_statement denotes We can expect the further studies on ACE2 functions to contribute toward a new therapy for organ damages that target this enzyme.
T32 10071-10151 Epistemic_statement denotes A recent report suggests that the Mas oncogene acts as a receptor for Ang-(1-7).
T33 10774-10948 Epistemic_statement denotes 36, 37 Recent studies suggest that Rac 1, c-Jun NH 2 -terminal kinase (JNK), p38 MAP kinase and the activation of phospholipase C might be involved in Mas-mediated signaling.
T34 11052-11190 Epistemic_statement denotes Moreover, in cardiomyocytes, an inhibition of MAP kinase activation by Ang-(1-7) can be blocked by antisense oligonucleotides against Mas.
T35 11191-11263 Epistemic_statement denotes 38 More detailed research works can show the Mas functions more clearly.
T36 11541-11631 Epistemic_statement denotes Moreover, the AT 2 -receptor agonists, such as compound 21, could be useful in the future.
T37 11749-11879 Epistemic_statement denotes However, it has been clarified that this pathway acts as a counter-regulation system against the ACE-Ang II-AT 1 receptor pathway.
T38 11880-12068 Epistemic_statement denotes Therefore, it is suggested that the ACE2-Ang-(1-7)-Mas axis could become a new target for the therapy of circulatory disorders and adult diseases, including that of the metabolic syndrome.
T39 12069-12168 Epistemic_statement denotes The total effects of RAS seem to stand on the balance between ACE and ACE2 activities ( Figure 4) .
T40 12169-12408 Epistemic_statement denotes In this respect, it could be considered that the classical ACE-Ang II-AT 1 receptor axis plays as a 'devil' and the 'ACE2-Ang-(1-7)-Mas axis' plays as an angel for fruitful aging in RAS through blood pressure lowering and organ protection.