Targeting RAGE to prevent SARS-CoV-2-mediated multiple organ failure: Hypotheses and perspectives

Life Sci. 2021 May 1:272:119251. doi: 10.1016/j.lfs.2021.119251. Epub 2021 Feb 23.

Abstract

A novel infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in December 2019 and declared as a global pandemic by the World Health. Approximately 15% of patients with COVID-19 progress to severe pneumonia and eventually develop acute respiratory distress syndrome (ARDS), septic shock and/or multiple organ failure with high morbidity and mortality. Evidence points towards a determinant pathogenic role of members of the renin-angiotensin system (RAS) in mediating the susceptibility, infection, inflammatory response and parenchymal injury in lungs and other organs of COVID-19 patients. The receptor for advanced glycation end-products (RAGE), a member of the immunoglobulin superfamily, has important roles in pulmonary pathological states, including fibrosis, pneumonia and ARDS. RAGE overexpression/hyperactivation is essential to the deleterious effects of RAS in several pathological processes, including hypertension, chronic kidney and cardiovascular diseases, and diabetes, all of which are major comorbidities of SARS-CoV-2 infection. We propose RAGE as an additional molecular target in COVID-19 patients for ameliorating the multi-organ pathology induced by the virus and improving survival, also in the perspective of future infections by other coronaviruses.

Keywords: COVID-19; HMGB1; RAGE; Renin-angiotensin system (RAS); SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • Animals
  • COVID-19 / complications*
  • COVID-19 / metabolism
  • COVID-19 / pathology
  • COVID-19 Drug Treatment
  • Drug Discovery*
  • Humans
  • Molecular Targeted Therapy
  • Multiple Organ Failure / etiology*
  • Multiple Organ Failure / metabolism
  • Multiple Organ Failure / pathology
  • Multiple Organ Failure / prevention & control*
  • Receptor for Advanced Glycation End Products / antagonists & inhibitors*
  • Receptor for Advanced Glycation End Products / metabolism
  • Renin-Angiotensin System / drug effects
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / physiology*
  • Signal Transduction / drug effects

Substances

  • Receptor for Advanced Glycation End Products