MicroRNA-155 modulation by renin-angiotensin system inhibitors may underlie their enigmatic role in COVID-19

Figure 1 Schematic interplay between microRNA-155/renin-angiotensin system/erythropoietin axis and influence of pharmacological renin-angiotensin system inhibition in severe acute respiratory coronavirus-2 infection. Hypoxia of any etiology elicits a hyperactive renin-angiotensin (Ang) system (RAS) and increases erythropoietin (EPO) production directly and via Ang II. MicroRNA-155 (miR-155) tames RAS hyperactivity via Ang II type 1 receptor (AT1R) repression. All these actions, pivotally regulated by miR-155 availability, collectively promote a protective cardiovascular phenotype and EPO evolutionary landscape that mediates severe acute respiratory coronavirus-2 resistance. Ang converting enzyme inhibitors and AT1R blockers block Ang II and the AT1R, respectively, and thereby impede EPO formation. Both also reduce miR-155 levels. ACE: Angiotensin converting enzyme; ACEi: Angiotensin converting enzyme inhibitors; ARB: Angiotensin II type 1 receptor blockers; AT1R: Angiotensin II type 1 receptor; EPO: Erythropoietin; MiR-155: MicroRNA-155; SARS-CoV-2: Severe acute respiratory coronavirus-2.