The Effect of a Non-peptide Angiotensin II type 2 receptor Agonist, Compound 21, on Aortic Aneurysm Growth in a Mouse Model of Marfan Syndrome

IntroductionAvailable evidence suggests that the renin-angiotensin-aldosterone (RAA) system is a good target for medical intervention on aortic root dilatation in Marfan syndrome (MFS). The effect of Compound 21 (C21), a non-peptide angiotensin II type 2 receptor (AT2R) agonist on aneurysm progression is was tested.MethodsMice with a mutation in fibrillin-1 (Fbn1C1039G/+) and wild-type (WT) mice were treated with vehicle, losartan, C21, enalapril or a combination. Blood pressure, aortic root diameter, and histological slides were evaluated.ResultsAll groups had a comparable blood pressure. Echographic evaluation of the aortic root diameter revealed a protective effect of angiotensin II type 1 receptor (AT1R) antagonist (losartan) and no effect of C21 treatment. None of the treatments had a beneficial effect on the histological changes in MFS.DiscussionThis study confirms that AT1R antagonism (losartan) decreases aortic aneurysm growth in a mouse model of Marfan syndrome. A non-peptide AT2R agonist (C21), at the doses studied, is was ineffective. Future studies are warranted to further elucidate the exact role of the RAA system in aneurysm formation in Marfan syndrome and identify alternative targets for intervention.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.status: publishe