Treatment with siRNA targeting Gper abrogated Ang
II-induced superoxide production (A). Comparable effects were observed using the
Nox1 downregulator G36 (B). Selectivity of G36 for the Nox1 isoform was
demonstrated by a reduction of Nox1 protein, but not Nox2 or Nox4 protein (C).
In contrast to wild-type cells (D), in vascular smooth muscle cells derived from
mice lacking Gper, Ang II was ineffective at stimulating
superoxide production (E). Conversely, adenoviral introduction of human Nox1
into cells from animals genetically lacking murine Gper
restored the cells’ ability to produce superoxide anion in response to
Ang II (F). Ang II, angiotensin II; siCTL, scrambled siRNA, siGPER, siRNA
against Gper; NDR, Nox1 downregulator. Gper+/+, wild-type;
Gper−/−, gper-deficient; tat, Nox1/2 inhibitor
gp91ds-tat; AdGFP, adenoviral vector carrying sequence for control protein GFP;
AdNox1, adenoviral vector carrying Nox1 sequence.
*p<0.05 vs. siCTL; *† and **p<0.05 vs CTL; ***p<0.05
vs solvent CTL; ****p<0.05 vs AdGFP control protein; Modified from
reference [25] and reproduced with
permission of the AAAS.