Thoracic aortic aneurysms (TAAs) are a potential life-threatening
disease with limited pharmacological treatment options. Current
treatment options are aimed at lowering aortic hemodynamic stress,
predominantly with beta-blockers. Increasing evidence supports a role
for the renin-angiotensin system (RAS) in aneurysm development. RAS
blockade would not only lower blood pressure, but might also target the
molecular pathways involved in aneurysm formation, in particular the
transforming growth factor-beta (TGF-β)- and extracellular
signalregulated kinase (ERK) 1/2 pathways. Indeed, the angiotensin II
type 1 (AT1) receptor blocker losartan was effective in lowering aortic
root growth in mice and patients with Marfan syndrome. RAS inhibition,
which is currently possible at three levels (renin, ACE and the AT1
receptor), is always accompanied by a rise in renin due to interference
with the negative feedback loop between renin and angiotensin II. Only
during AT1 receptor blockade will this result in stimulation of the
non-blocked angiotensin II type 2 (AT2) receptor. This review
summarizes the clinical aspects of TAAs, provides an overview of the
current mouse models for TAAs, and focuses on the RAS as a new target
for TAA treatment, discussing in particular the possibility that AT2
receptor stimulation might be crucial in this regard. If true, this
would
imply that AT1 receptor blockers (and not ACE inhibitors or renin
inhibitors) should be the preferred treatment option for TAAs.http://repub.eur.nl/res/pub/22789/Moltzer_Omslag.pdf
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