Perindopril decreases angiotensin-converting enzyme 2 (ACE2) expression in human adipocytes exposed to SARS-CoV-2 S1 spike protein

Narra J. 2024 Aug;4(2):e746. doi: 10.52225/narra.v4i2.746. Epub 2024 May 2.

Abstract

The expression of angiotensin-converting enzyme 2 (ACE2) in the adipose tissues of obese patients needs further study, as it may aid infection and serve as a viral reservoir. There has been controversy over whether to use ACE inhibitors to prevent coronavirus disease 2019 (COVID-19) severity. Perindopril, an ACE2 inhibitor, has been proposed; however, its relationship with COVID-19 has not yet been clear. The aim of this study was to investigate the effect of perindopril to reduce the expression of ACE2 and pro-inflammatory cytokine in adipocytes exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Enzymatic isolation of adipose tissues was performed from obese male donor patients aged 30-50 years, then exposed it with SARS-CoV-2 S1 spike protein. This study also included human recombinant ACE2 (hrsACE2) as a comparison to perindopril. The expression of ACE2 was evaluated using ELISA. Our data indicated that SARS-CoV-2 Spike protein exposure increased ACE2 expression significantly. Administration of perindopril decreased ACE2 expression (43.37 μg/mL) significantly compared to the positive group (80.31 μg/mL) (p<0.001). Perindopril administration also decreased IL-6 levels significantly compared to positive group (p<0.001). This study highlights that perindopril could reduce the ACE2 expression and pro-inflammatory cytokine levels in adipocytes exposed to SARS-CoV-2 S1 spike protein.

Keywords: ACE2; IL-6; SARS-CoV-2; obesity; perindopril.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes* / drug effects
  • Adipocytes* / metabolism
  • Adipocytes* / virology
  • Adult
  • Angiotensin-Converting Enzyme 2* / genetics
  • Angiotensin-Converting Enzyme 2* / metabolism
  • Angiotensin-Converting Enzyme Inhibitors* / pharmacology
  • COVID-19* / metabolism
  • COVID-19* / virology
  • Cytokines / metabolism
  • Humans
  • Male
  • Middle Aged
  • Obesity / drug therapy
  • Obesity / metabolism
  • Perindopril* / pharmacology
  • SARS-CoV-2 / drug effects
  • Spike Glycoprotein, Coronavirus* / metabolism

Substances

  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors
  • Cytokines
  • Perindopril
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2