Published in:
01-04-2015 | Original Research Paper
ACE2 and Ang-(1–7) protect endothelial cell function and prevent early atherosclerosis by inhibiting inflammatory response
Published in: Inflammation Research | Issue 3-4/2015
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Background
Angiotensin-converting enzyme 2 (ACE2) is a counter-regulator against ACE by converting angiotensin II (Ang-II) to Ang-(1–7), but the effect of ACE2 and Ang-(1–7) on endothelial cell function and atherosclerotic evolution is unknown. We hypothesized that ACE2 overexpression and Ang-(1–7) may protect endothelial cell function by counterregulation of angiotensin II signaling and inhibition of inflammatory response.
Methods
We used a recombinant adenovirus vector to locally overexpress ACE2 gene (Ad-ACE2) in human endothelial cells in vitro and in apoE-deficient mice in vivo. The Ang II-induced MCP-1, VCAM-1 and E-selectin expression, endothelial cell migration and adhesion of human monocytic cells (U-937) to HUVECs by ACE2 gene transfer were evaluated in vitro. Accelerated atherosclerosis was studied in vivo, and atherosclerosis was induced in apoE-deficient mice which were divided randomly into four groups that received respectively a ACE2 gene transfer, Ad-ACE2, Ad-EGFP, Ad-ACE2 + A779, an Ang-(1–7) receptor antagonist, control group. After a gene transfer for 4 weeks, atherosclerotic pathology was evaluated.
Results
ACE2 gene transfer not only promoted HUVECs migration, inhibited adhesion of monocyte to HUVECs and decreased Ang II-induced MCP-1, VCAM-1 and E-selectin protein production in vitro, but also decreased the level of MCP-1, VCAM-1 and interleukin 6 and inhibit atherosclerotic plaque evolution in vivo. Further, administration of A779 increased the level of MCP-1, VCAM-1 and interleukin 6 in vivo and led to further advancements in atherosclerotic extent.
Conclusions
ACE2 and Ang-(1–7) significantly inhibit early atherosclerotic lesion formation via protection of endothelial function and inhibition of inflammatory response.