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

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.