Severe acute respiratory coronavirus-2(SARS-CoV-2)infection course differs between the young and healthy and the elderly with co-morbidities.In the latter a potentially lethal coronavirus disease 2019(COVID-19)cytokin...Severe acute respiratory coronavirus-2(SARS-CoV-2)infection course differs between the young and healthy and the elderly with co-morbidities.In the latter a potentially lethal coronavirus disease 2019(COVID-19)cytokine storm has been described with an unrestrained renin-angiotensin(Ang)system(RAS).RAS inhibitors[Ang converting enzyme inhibitors and Ang II type 1 receptor(AT1R)blockers]while appearing appropriate in COVID-19,display enigmatic effects ranging from protection to harm.MicroRNA-155(miR-155)-induced translational repression of key cardiovascular(CV)genes(i.e.,AT1R)restrains SARS-CoV-2-engendered RAS hyperactivity to tolerable and SARS-CoV-2-protective CV phenotypes supporting a protective erythropoietin(EPO)evolutionary landscape.MiR-155’s disrupted repression of the AT1R 1166C-allele associates with adverse CV and COVID-19 outcomes,confirming its decisive role in RAS modulation.RAS inhibition disrupts this miR-155-EPO network by further lowering EPO and miR-155 in COVID-19 with co-morbidities,thereby allowing unimpeded RAS hyperactivity to progress precariously.Current pharmacological interventions in COVID-19 employing RAS inhibition should consider these complex but potentially detrimental miR-155/EPO-related effects.展开更多
文摘Severe acute respiratory coronavirus-2(SARS-CoV-2)infection course differs between the young and healthy and the elderly with co-morbidities.In the latter a potentially lethal coronavirus disease 2019(COVID-19)cytokine storm has been described with an unrestrained renin-angiotensin(Ang)system(RAS).RAS inhibitors[Ang converting enzyme inhibitors and Ang II type 1 receptor(AT1R)blockers]while appearing appropriate in COVID-19,display enigmatic effects ranging from protection to harm.MicroRNA-155(miR-155)-induced translational repression of key cardiovascular(CV)genes(i.e.,AT1R)restrains SARS-CoV-2-engendered RAS hyperactivity to tolerable and SARS-CoV-2-protective CV phenotypes supporting a protective erythropoietin(EPO)evolutionary landscape.MiR-155’s disrupted repression of the AT1R 1166C-allele associates with adverse CV and COVID-19 outcomes,confirming its decisive role in RAS modulation.RAS inhibition disrupts this miR-155-EPO network by further lowering EPO and miR-155 in COVID-19 with co-morbidities,thereby allowing unimpeded RAS hyperactivity to progress precariously.Current pharmacological interventions in COVID-19 employing RAS inhibition should consider these complex but potentially detrimental miR-155/EPO-related effects.
