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In‐vitro and in‐vivo ACE2 gene delivery: evidence for a role in the central regulation of blood pressure
Author(s) -
Feng Yumei,
Yue Xinping,
Hickman Peter,
Lazartigues Eric
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a889-c
Subject(s) - in vivo , western blot , green fluorescent protein , in vitro , cytoplasm , biology , microbiology and biotechnology , chemistry , gene , biochemistry , genetics
We recently reported ACE2 presence in brain regions controlling cardiovascular (CV) function. However, the role of ACE2 in CV regulation remains unclear due to the lack of specific tools to investigate its function. To selectively manipulate ACE2 expression in specific organs or cells, we developed a highly efficient adenovirus coding for human ACE2 with a GFP tag (Ad‐ACE2). Neuronal and vascular smooth muscle cells were infected with Ad‐ACE2 (0–200 MOI) or Ad‐GFP (control) then infection efficiency (GFP fluorescence), ACE2 protein expression (western‐blot) and activity (fluorometric assay) were monitored. Besides dose‐dependent high protein and activity levels, our results show expression of hACE2 in the cytoplasm and a secreted form in the medium. In‐vivo, Ad‐ACE2 infection (2x10 6 pfu icv) shows a time‐dependent expression of ACE2 protein and activity in mouse brain beyond 2 wks. In addition, 7 days after virus infection, the pressor response (mmHg) to icv AngII (200 pmol) was significantly reduced in Ad‐ACE2‐ (15±2; n=4) compared to Ad‐GFP‐treated (26±3; n=3) mice ( P <0.05). These data show that Ad‐ACE2 can be used successfully to manipulate ACE2 expression and activity in‐vitro and in‐vivo. Moreover, our results establish a role for ACE2 in the central regulation of CV function, offering a new target for the treatment of hypertension and other CV diseases. Support: NIH NS052479 and P20 RR018766.