Aortic Pathology and the Role of the Renin-Angiotensin System
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.
|Keywords||aneurysms, cardioloy, enin-angiotenin, pathology, thorax, vascular diseases|
|Promotor||Roos-Hesselink, J.W. (Jolien) , Danser, A.H.J. (Jan)|
|Publisher||Erasmus University Rotterdam|
|Sponsor||Netherlands Heart Foundation, Stichting Lijf en Leven, Erasmus University Rotterdam, J.E. Jurriaanse Stichting, Heart Medical Europe BV, Sanovi-Aventis Netherlands BV, AstraZenica BV, Novartis Pharma BV|
Moltzer, E.. (2011, March 23). Aortic Pathology and the Role of the Renin-Angiotensin System. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/22789