The pivotal role of the angiotensin-II–NF-κB axis in the development of COVID-19 pathophysiology

Okamoto, Hiroshi; Ichikawa, Naomi

doi:10.1038/s41440-020-00560-7

Cited by 23 publications

(19 citation statements)

References 8 publications

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“…A heterozygote loss of ACE2 might be adequate to rise exposure towards heart disease [ 4 ]. In individuals with different health issues, the viral invasion may take full advantage of this deficiency for causing inflammation and pulmonary complications and augment the unevenness between the ACE → angiotensin II → AT1 receptor pole (detrimental) and the ACE-2 → angiotensin 1-7 → AT2 and Mas receptor pole (protective) [ 4 , 78 ]. Hence, ACE-2 inhibitors and AT1 blockers might be established as promising therapeutic strategies in COVID-19 treatment.…”

Section: Recent Research Advancement Oface-2 Related To Covid-19mentioning

confidence: 99%

Understanding the role of ACE-2 receptor in pathogenesis of COVID-19 disease: a potential approach for therapeutic intervention

et al. 2021

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Angiotensin-converting enzyme (ACE) and its homologue, ACE2, are commonly allied with hypertension, renin–angiotensin–aldosterone system pathway, and other cardiovascular system disorders. The recent pandemic of COVID-19 has attracted the attention of numerous researchers on ACE2 receptors, where the causative viral particle, SARS-CoV-2, is established to exploit these receptors for permitting their entry into the human cells. Therefore, studies on the molecular origin and pathophysiology of the cell response in correlation to the role of ACE2 receptors to these viruses are bringing novel theories. The varying level of manifestation and importance of ACE proteins, underlying irregularities and disorders, intake of specific medications, and persistence of assured genomic variants at the ACE genes are potential questions raising nowadays while observing the marked alteration in response to the SARS-CoV-2-infected patients. Therefore, the present review has focused on several raised opinions associated with the role of the ACE2 receptor and its impact on COVID-19 pathogenesis.

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Section: Recent Research Advancement Oface-2 Related To Covid-19mentioning

confidence: 99%

Understanding the role of ACE-2 receptor in pathogenesis of COVID-19 disease: a potential approach for therapeutic intervention

et al. 2021

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“…Intriguingly, a dysregulated RAS can produce a similar immunologic fingerprint. For example, unopposed AT2, likely via its functional interaction with NFκB and subsequent upregulation of IL-6, could play an active role in “cytokine storm” [ 102 , 103 ]. Extrapolating from our discussion above, AT2 may exert direct inhibitory effects on T-cell function – perhaps an explanation for the leukopenia seen in COVID-19 patients [ 88 ].…”

Section: Evidence For Ace2 Downregulation Modelmentioning

confidence: 99%

Functional ACE2 deficiency leading to angiotensin imbalance in the pathophysiology of COVID-19

Cook

Ausiello

2021

Rev Endocr Metab Disord

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SARS-CoV-2, the virus responsible for COVID-19, uses angiotensin converting enzyme 2 (ACE2) as its primary cell-surface receptor. ACE2 is a key enzyme in the counter-regulatory pathway of the broader renin-angiotensin system (RAS) that has been implicated in a broad array of human pathology. The RAS is composed of two competing pathways that work in opposition to each other: the “conventional” arm involving angiotensin converting enzyme (ACE) generating angiotensin-2 and the more recently identified ACE2 pathway that generates angiotensin (1–7). Following the original SARS pandemic, additional studies suggested that coronaviral binding to ACE2 resulted in downregulation of the membrane-bound enzyme. Given the similarities between the two viruses, many have posited a similar process with SARS-CoV-2. Proponents of this ACE2 deficiency model argue that downregulation of ACE2 limits its enzymatic function, thereby skewing the delicate balance between the two competing arms of the RAS. In this review we critically examine this model. The available data remain incomplete but are consistent with the possibility that the broad multisystem dysfunction of COVID-19 is due in large part to functional ACE2 deficiency leading to angiotensin imbalance with consequent immune dysregulation and endothelial cell dysfunction.

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“…In turn, the activated STAT3 and NF-kB further stimulate the IL-6 amplifier to activate NF-kB, thus forming a positive feedback loop that leads to deteriorated inflammation (75). On the other hand, the AngII-AT1R axis promotes the formation of membrane-associated guanylate kinase-like protein, B-cell lymphoma 10, and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (CBM) signalosome (76). CBM signalosome activates IkB kinase complex to induce the phosphorylation and degradation of IkB, leading to NF-kB activation (76).…”

Section: Inflammation and Nf-kb In Covid-19mentioning

confidence: 99%

“…On the other hand, the AngII-AT1R axis promotes the formation of membrane-associated guanylate kinase-like protein, B-cell lymphoma 10, and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (CBM) signalosome (76). CBM signalosome activates IkB kinase complex to induce the phosphorylation and degradation of IkB, leading to NF-kB activation (76).…”

Section: Inflammation and Nf-kb In Covid-19mentioning

confidence: 99%

Comparison of COVID-19 and Lung Cancer via Reactive Oxygen Species Signaling

2021

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COVID-19 and lung cancer are two severe pulmonary diseases that cause millions of deaths globally each year. Understanding the dysregulated signaling pathways between them can benefit treating the related patients. Recent studies suggest the critical role of reactive oxygen species (ROS) in both diseases, indicating an interplay between them. Here we reviewed references showing that ROS and ROS-associated signaling pathways, specifically via NRF2, HIF-1, and Nf-κB pathways, may bridge mutual impact between COVID-19 and lung cancer. As expected, typical ROS-associated inflammation pathways (HIF-1 and Nf-κB) are activated in both diseases. The activation of both pathways in immune cells leads to an overloading immune response and exacerbates inflammation in COVID-19. In lung cancer, HIF-1 activation facilitates immune escape, while Nf-κB activation in T cells suppresses tumor growth. However, the altered NRF2 pathway show opposite trends between them, NRF2 pathways exert immunosuppressive effects in both diseases, as it represses the immune response in COVID-19 patients while facilitates the immune escape of tumor cells. Furthermore, we summarized the therapeutic targets (e.g., phytochemicals) on these ROS pathways. In sum, our review focus on the understanding of ROS Signaling in COVID-19 and lung cancer, showing that modulating ROS signaling pathways may alleviate the potentially mutual impacts between COVID-19 and lung cancer patients.

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The pivotal role of the angiotensin-II–NF-κB axis in the development of COVID-19 pathophysiology

Cited by 23 publications

References 8 publications

Understanding the role of ACE-2 receptor in pathogenesis of COVID-19 disease: a potential approach for therapeutic intervention

Understanding the role of ACE-2 receptor in pathogenesis of COVID-19 disease: a potential approach for therapeutic intervention

Functional ACE2 deficiency leading to angiotensin imbalance in the pathophysiology of COVID-19

Comparison of COVID-19 and Lung Cancer via Reactive Oxygen Species Signaling

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