Association of polymorphisms in serotonin and nitric oxide genes with clinical outcome of dengue in Brazilian northeast population

Santos, Ana Caroline Melo dos; Moura, Edilson Leite de; Silva, Denise Macedo da; Moura, Alexandre Wendell Araujo; Ferreira, Jean Moisés; Neto, Abel Barbosa Lira; Silva, Aline Cristine Pereira e; Alves, Verônica de Medeiros; Balliano, Tatiane Luciano; Farias, Karol Fireman de; Filho, José Luiz de Lima; Figueiredo, Elaine Virgínia Martins de Souza

doi:10.1016/j.actatropica.2018.11.015

Cited by 3 publications

(1 citation statement)

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“…These early age, physiological states, in certain individuals also serendipitously enhanced by RAAS activating SNPs, elevate ACE1 and would appear to promote a tolerable RAAS hyperactivity, that through elevated Ang II and ALD, both known master regulators of EPO secretion, can plausibly account for the elevated EPO levels seen in the young [31][32][33][34][35]. All molecules in this early age protective evolutionary landscape, involving RAAS-EPO-eNOS interactions, are under significant genetic control aiming to support, augment, and extend EPO elevation and eNOS activity upon pathogen insult, as witnessed by the thalassemias, and protective RAAS and eNOS single nucleotide polymorphisms (SNPs) in malaria and Dengue virus (DENV) infection [27,31,32,[38][39][40]. The resulting elevated EPO levels and the consequently enhanced EPO-eNOS/NO pathway responsiveness, are associated with a better outcome in children with cerebral malaria and may reasonably also promote an early age protection against SARS-CoV-2; indeed, children below the age of 5, when EPO response is maximal, generally experience asymptomatic or mild SARS-CoV-2 infections [4,[30][31][32][41][42][43][44][45].…”

Section: Introductionmentioning

confidence: 99%

Beauty and the beast: host microRNA-155 versus SARS-CoV-2

Papadopoulos

Papadopoulou

2023

Human Cell

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Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection in the young and healthy usually results in an asymptomatic or mild viral syndrome, possibly through an erythropoietin (EPO)-dependent, protective evolutionary landscape. In the old and in the presence of co-morbidities, however, a potentially lethal coronavirus disease 2019 (COVID-19) cytokine storm, through unrestrained renin-angiotensin aldosterone system (RAAS) hyperactivity, has been described. Multifunctional microRNA-155 (miR-155) elevation in malaria, dengue virus (DENV), the thalassemias, and SARS-CoV-1/2, plays critical antiviral and cardiovascular roles through its targeted translational repression of over 140 genes. In the present review, we propose a plausible miR-155-dependent mechanism whereby the translational repression of AGRT1 , Arginase-2 and Ets-1 , reshapes RAAS towards Angiotensin II (Ang II) type 2 (AT2R)-mediated balanced, tolerable, and SARS-CoV-2-protective cardiovascular phenotypes. In addition, it enhances EPO secretion and endothelial nitric oxide synthase activation and substrate availability, and negates proinflammatory Ang II effects. Disrupted miR-155 repression of AT1R + 1166C-allele, significantly associated with adverse cardiovascular and COVID-19 outcomes, manifests its decisive role in RAAS modulation. BACH1 and SOCS1 repression creates an anti-inflammatory and cytoprotective milieu, robustly inducing antiviral interferons. MiR-155 dysregulation in the elderly, and in comorbidities, allows unimpeded RAAS hyperactivity to progress towards a particularly aggressive COVID-19 course. Elevated miR-155 in thalassemia plausibly engenders a favorable cardiovascular profile and protection against malaria, DENV, and SARS-CoV-2. MiR-155 modulating pharmaceutical approaches could offer novel therapeutic options in COVID-19.

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