LitCovid-sentences  

PMC:7534795 / 98719-106778 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T625 0-104 Sentence denotes 8.4 Role of n-3 PUFAs in modulating the renin-angiotensin aldosterone system in the setting of COVID-19
T626 105-249 Sentence denotes The renin-angiotensin aldosterone system (RAAS) is a key regulator of vascular function modulating natriuresis, blood volume and blood pressure.
T627 250-387 Sentence denotes Briefly, angiotensin I (Ang I) is metabolized by angiotensin-converting enzyme (ACE) to form the vasoconstrictor angiotensin II (Ang II).
T628 388-711 Sentence denotes Accumulation, prolonged and excessive binding of Ang II to the angiotensin 1 receptor in the heart and blood vessels mediates several effects which include vasoconstriction, hypertension, cardiac hypertrophy, increased ROS production and adverse fibrosis (Fyhrquist, Metsarinne, & Tikkanen, 1995; Perazella & Setaro, 2003).
T629 712-933 Sentence denotes Earlier literature demonstrated Ang II may act as a proinflammatory cytokine potentially having a significant role in cardiac remodeling (Gibbons, Pratt, & Dzau, 1992; Griendling, Minieri, Ollerenshaw, & Alexander, 1994).
T630 934-1299 Sentence denotes Conversely, the master regulator ACE2, a type 1 integral membrane glycoprotein expressed in most tissues including the lungs, kidneys, heart and vascular endothelium layers, can metabolize Ang II to produce the vasodilator angiotensin (Ang 1–7) which protects the cardiovascular system against the actions of Ang II (Das, 2018; Kumar & Das, 1997; Yan et al., 2020).
T631 1300-1669 Sentence denotes Beside its vasodilatory properties, Ang-(1–7) promotes resolution of inflammation by decreasing TNF-α, IL-6, vascular adhesion molecule, monocyte chemoattractant protein-1 and macrophage infiltration enhancing the survival of cardiomyocytes and endothelial cells during severe immune responses (Simoes e Silva, Silveira, Ferreira, & Teixeira, 2013; Zhang et al., 2015).
T632 1670-1888 Sentence denotes Accordingly, several clinical and experimental studies reported dysregulation of RAAS due to increased Ang II and decreased ACE2 can lead to detrimental inflammatory responses and worsening of cardiovascular disorders.
T633 1889-2201 Sentence denotes Therefore, maintaining the activity of ACE2 is essential in preserving the balance of the RAAS and effects on vasoconstriction, sodium retention and fibrosis and may elicit protective effects against hypertension, HF, MI and other CVDs (Crackower et al., 2002; Patel et al., 2016; Wang, Gheblawi, & Oudit, 2020).
T634 2202-2313 Sentence denotes Recent evidence has demonstrated SARS-CoV-2 uses ACE2 as an internalization receptor to enter the target cells.
T635 2314-2535 Sentence denotes The spike (S) glycoprotein of SARS-CoV-2 recognizes and interacts with its target ACE2 receptor on the host cell surface, mediating viral entry during the infection cycle (Letko, Marzi, & Munster, 2020; Yan et al., 2020).
T636 2536-2644 Sentence denotes Excessive binding of spike protein to ACE2 leads to downregulation of the ACE2 receptor (Jung et al., 2020).
T637 2645-2792 Sentence denotes This finding is consistent with reports in the animal models infected with SARS-CoV (Crackower et al., 2002; Imai et al., 2005; Kuba et al., 2005).
T638 2793-2988 Sentence denotes The reduction in ACE2 levels leads to excessive pro-inflammatory responses adversely affecting both lung and cardiovascular systems (Crackower et al., 2002; Imai et al., 2005; Kuba et al., 2005).
T639 2989-3216 Sentence denotes These detrimental effects can be explained as the partial decrease in ACE2 function leads to dominant angiotensin II effects, including augmented cytokine storm, inflammation, vasoconstriction and susceptibility for thrombosis.
T640 3217-3414 Sentence denotes These effects further increase the cardiovascular burden by worsening hypertension, HF and other cardiovascular disorders in predisposed patients (Liu, Blet, Smyth, & Li, 2020; Oudit et al., 2009).
T641 3415-3530 Sentence denotes Importantly, the accumulation of Ang II was positively associated to viral load and lung injury (Liu et al., 2020).
T642 3531-3803 Sentence denotes Moreover, reduction in the activity and/or number of ACE2 leads to deficiency of Ang-(1–7) production and consequently loss of its anti-inflammatory, vasodilatory, and cardiovascular protective effects (Lelis, Freitas, Machado, Crespo, & Santos, 2019; Patel et al., 2016).
T643 3804-3941 Sentence denotes Therefore, it is hypothesized that inhibition of RAAS may be helpful to attenuate the inflammatory storm and ameliorate end-organ damage.
T644 3942-4224 Sentence denotes Interestingly, recent data indicates individuals with COVID-19 who are being treated with ACE inhibitors or ARBs, for pre-existing conditions, are at lower risk of 28-day all-cause mortality than those not treated with ACE inhibitors or ARBs (Wang et al., 2020; Zhang et al., 2020).
T645 4225-4471 Sentence denotes Although ARBs and ACE inhibitors do not directly impact ACE2, they indirectly elevate ACE2 activity and the beneficial Ang-(1–7) production and counter the excessive production of the harmful Ang II (Hanff, Harhay, Brown, Cohen, & Mohareb, 2020).
T646 4472-4654 Sentence denotes Therefore, it was proposed that maintaining the levels of ACE2 and its downstream effector Ang-(1–7) may limit cardiovascular damage secondary to COVID-19 (Wang, Edin, et al., 2020).
T647 4655-4779 Sentence denotes Interestingly, several reports showed that n-3 PUFAs can regulate the RAAS system by modulating both Ang II and ACE2 levels.
T648 4780-5023 Sentence denotes For instance, emerging literature indicates n-3 PUFAs and their endogenously generated metabolites can directly reduce the expression and activity of ACE, thereby reducing angiotensin II formation and cardiovascular burden (Kumar & Das, 1997).
T649 5024-5229 Sentence denotes Moreover, it has been demonstrated that supplementation of mice with an n-3 PUFA rich diet for three weeks resulted in attenuated Ang-II-induced blood pressure via up-regulation of ACE2 (Ulu et al., 2013).
T650 5230-5506 Sentence denotes Alternatively, as previously discussed, incorporation of n-3 PUFAs into the cell membranes will alter key properties, which can consequently affect protein number and affinity of SARS-CoV-2 to ACE2 (Candelario & Chachisvilis, 2013; Das, 1999, Das, 2020b; Glende et al., 2008).
T651 5507-5800 Sentence denotes Together, these studies suggest a novel role for n-3 PUFAs in regulating SARS-CoV-2 infection where the potential benefit as an adjuvant therapy involves increasing the production of Ang-(1–7) and reducing the levels of Ang II, thereby limiting COVID-19-triggered cardiovascular complications.
T652 5801-5970 Sentence denotes Importantly, evidence demonstrating upregulation and enhanced activity of ACE2 suggested it will facilitate the infectivity of SARS-CoV-2 (South, Diz, & Chappell, 2020).
T653 5971-6117 Sentence denotes Accordingly, some researchers proposed that ACE inhibitors and ARBs should be discontinued in COVID-19 patients (Diaz, 2020; Esler & Esler, 2020).
T654 6118-6322 Sentence denotes However, in addition to the direct effects on cardiac ACE2 other mechanisms such as triggering a cytokine storm will markedly contribute to SARS-CoV-2-induced injury (Chen, Li, Chen, Feng, & Xiong, 2020).
T655 6323-6558 Sentence denotes A recent study conducted by Yang et al., demonstrated COVID-19 patients with hypertension using ACE inhibitors/ARBs had lower mortality rates than hypertensive COVID-19 patients that were not on ACE inhibitors/ARBs (Yang et al., 2020).
T656 6559-6755 Sentence denotes Moreover, Mancia et al. examined 6272 patients and found no association between RAAS inhibitor use and susceptibility or development of COVID-19 (Mancia, Rea, Ludergnani, Apolone, & Corrao, 2020).
T657 6756-7000 Sentence denotes In that sense, a published statement by American Heart Association (AHA), the American College of Cardiology (ACC) and the Heart Failure Society of America strongly recommended continuation of ACE inhibitor/ARBs (Zhang, Zhu, Cai, et al., 2020).
T658 7001-7280 Sentence denotes Together, these data suggest therapies targeting ACE and Ang II do not appear to increase the likelihood of SARS-CoV-2 infection, but may have a role in abrogating the inflammatory response and vasoconstriction that contributes to the clinical deterioration in COVID-19 patients.
T659 7281-7477 Sentence denotes In summary, evidence has demonstrated infection with SARS-CoV-2 induces internalization and downregulation of ACE2, which may aggravate a patient's condition by limiting the degradation of Ang II.
T660 7478-7742 Sentence denotes Elevated Ang II levels induce several detrimental effects on the cardiovascular system including elevated blood pressure, excessive recruitment and infiltration of inflammatory immune cells to the heart as well as increased secretion of pro-inflammatory cytokines.
T661 7743-7896 Sentence denotes Reduced ACE2 levels are associated with decreased formation of Ang-(1–7) and thus loss of its vasodilatory, anti-inflammatory and CVD-protective effects.
T662 7897-8059 Sentence denotes Therefore, intervention with treatments to correct an imbalance in the RAAS system, such as ACE inhibitors, ARBs and n-3 PUFAs, can possibly improve the outcomes.