Key result
Inhibition or deficiency of Ets-1 significantly blunted Angiotensin II-induced reactive oxygen species production and medial hypertrophy in mice and human aortic smooth muscle cells.
Why the study?
Does Ets-1 inhibition reduce Angiotensin II-induced reactive oxygen species generation and medial hypertrophy in preclinical models?
Does Ets-1 inhibition reduce Angiotensin II-induced reactive oxygen species generation and medial hypertrophy in preclinical models?
Ets-1 functions as a critical downstream transcriptional mediator of Ang II-induced ROS generation, highlighting its potential as a therapeutic target for vascular inflammation.
Ets-1 inhibition merits exploration in vascular remodeling; leaves open translation to clinical hypertension or atherosclerosis therapies.
Angiotensin (Ang) II is a potent mediator of vascular inflammation. A central mechanism by which Ang II promotes inflammation is through the generation of reactive oxygen species (ROS). In the current study, we investigated the role of the transcription factor Ets-1 in regulating Ang II-induced ROS generation. ROS generation was measured in the thoracic aorta of Ets-1(-/-) mice compared with littermate controls after continuous infusion of Ang II. H2O2 and superoxide anion (O2(-)) production were significantly blunted in the Ets-1(-/-) mice. Inhibition of Ets-1 expression by small interfering RNA in primary human aortic smooth muscle cells also potently inhibited ROS production and the induction of the NAD(P)H oxidase subunit p47(phox) in response to Ang II. To evaluate the therapeutic potential of inhibiting Ets-1 in wild-type mice, dominant negative Ets-1 membrane-permeable peptides were administered systemically. Ang II-induced ROS production and medial hypertrophy in the thoracic aorta were markedly diminished as a result of blocking Ets-1. In summary, Ets-1 functions as a critical downstream transcriptional mediator of Ang II ROS generation by regulating the expression of NAD(P)H oxidase subunits such as p47(phox).
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Ni et al. (2007) studied Angiotensin II-induced vascular inflammation. Ets-1 inhibition (genetic knockout, siRNA, or dominant negative peptides) vs. Littermate controls or untreated wild-type mice/cells was evaluated on Reactive oxygen species (ROS) generation and p47(phox) expression. Inhibition or deficiency of Ets-1 significantly blunted Angiotensin II-induced reactive oxygen species production and medial hypertrophy in mice and human aortic smooth muscle cells.
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