title: The role of the renin-angiotensin system in thoracic aortic aneurysms: clinical implications.
abstract: 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 β-adrenoceptor 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-β and extracellular signal-regulated kinase 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's syndrome. RAS inhibition (currently possible at 3 levels, i.e. 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.
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Els
authors.initials: E
authors.lastname: Moltzer
authors.forename: Jeroen
authors.initials: J
authors.lastname: Essers
authors.forename: Joep H M
authors.initials: JH
authors.lastname: van Esch
authors.forename: Jolien W
authors.initials: JW
authors.lastname: Roos-Hesselink
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000188:drug therapy* / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D006801:Humans; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers