ACE2 overexpression inhibits angiotensin II-induced monocyte chemoattractant protein-1 expression in macrophages

Arch Med Res. 2008 Feb;39(2):149-54. doi: 10.1016/j.arcmed.2007.07.010. Epub 2007 Oct 31.

Abstract

Background: The discovery of angiotensin-converting enzyme 2 (ACE2) has shed light on the potential therapy for cardiovascular disease, owing to its key role in the formation of vasoprotective peptide angiotensin (Ang 1-7) from angiotensin (Ang) II. The aim of this study was to evaluate whether ACE2 overexpression could protect human monocyte cell line (THP-1) macrophages from angiotensin II-induced monocyte chemoattractant protein-1 (MCP-1) formation.

Methods: A truncated form of mouse ACE2 (mACE2) was cloned into adenovirus vector (Ad-ACE2) and transfected into THP-1. We examined expression of MCP-1 by administration of a selected Ang (1-7) antagonist (A779) to show the effect of ACE2 overexpression on MCP-1 level induced by AngII.

Results: AngII-induced MCP-1 expression increased obviously at 24 h and at the concentration of 10(-6) M. Transduction of THP-1 with Ad-ACE2 resulted in a viral increase in ACE2 activity. This was associated with a significant attenuation of AngII-induced MCP-1 production by 39.6+/-4.0% in THP-1 (mean+/-SEM, n=3). Moreover, expression of MCP-1 increased by 35.1+/-4.2% in Ad-ACE2 transfected THP-1 after incubation with Ang II and A779 compared to that with AngII alone. Collectively, these results indicated that ACE2 overexpression in the THP-1 attenuates AngII-induced MCP-1 production and that this reduction is likely mediated by increased Ang (1-7) level.

Conclusions: ACE2 overexpression may provide a new therapeutic strategy for atherosclerosis by inhibiting MCP-1 production induced by AngII.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I
  • Angiotensin II / antagonists & inhibitors
  • Angiotensin II / metabolism*
  • Angiotensin II / pharmacology
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism
  • Cell Line
  • Chemokine CCL2 / biosynthesis*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Humans
  • Mice
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Peptidyl-Dipeptidase A / metabolism*

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Peptide Fragments
  • Angiotensin II
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)