ACE2 Overexpression Inhibits Angiotensin II-induced Monocyte Chemoattractant Protein-1 Expression in Macrophages

Background scovery 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. s cated 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. s 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. sions verexpression may provide a new therapeutic strategy for atherosclerosis by inhibiting MCP-1 production induced by AngII.