PDF(Pubmed)
Abstract：
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.
摘要：
严重的急性呼吸道冠状病毒2（SARS-CoV-2）感染在年轻和健康通常导致无症状或轻度病毒综合征，可能通过促红细胞生成素（EPO）依赖性，保护性进化景观。在旧的和存在合并症的情况下，然而,2019年可能致命的冠状病毒病（COVID-19）细胞因子风暴，通过不受约束的肾素-血管紧张素-醛固酮系统（RAAS）过度活动，已被描述。疟疾中的多功能microRNA-155（miR-155）升高，登革热病毒（DENV），地中海贫血，和SARS-CoV-1/2，通过其对140多个基因的靶向翻译抑制发挥关键的抗病毒和心血管作用。在本次审查中，我们提出了一种似乎合理的miR-155依赖性机制，由此AGRT1，精氨酸酶-2和Ets-1的翻译抑制重塑RAAS朝向血管紧张素II（AngII）2型（AT2R）介导的平衡，可容忍,和SARS-CoV-2保护性心血管表型。此外,它增强EPO分泌和内皮型一氧化氮合酶激活和底物可用性，并消除促炎AngII效应。AT1R+1166C等位基因的miR-155抑制中断，与不良心血管和COVID-19结局显着相关，体现了其在RAAS调制中的决定性作用。BACH1和SOCS1抑制产生抗炎和细胞保护环境，强烈诱导抗病毒干扰素。MiR-155在老年人中的失调，在合并症中，允许畅通无阻的RAAS多动症进展为特别积极的COVID-19疗程。地中海贫血中miR-155的升高可能会产生良好的心血管状况和对疟疾的保护作用，DENV,和SARS-CoV-2.MiR-155调节药物方法可以为COVID-19提供新的治疗选择。
