enalapril and Marfan-Syndrome

Despite variable clinical results, beta blockers have become the primary therapy for prevention of aortic dilation in patients with the Marfan syndrome. This study examines the use of the angiotensin-converting enzyme inhibitor enalapril for treatment of these patients. We sought to examine the effects of enalapril versus beta-blocker therapy in patients with the Marfan syndrome and noted improved aortic distensibility (3.0 +/- 0.3 vs 1.9 +/- 0.4 cm2 dynes(-1); p <0.02) and a reduced aortic stiffness index (8.0 +/- 2.9 vs 18.4 +/- 3.8; p <0.05) in patients receiving enalapril compared with those receiving beta blockers. These favorable hemodynamic changes were associated with a smaller increase in aortic root diameter (0.1 +/- 1.0 vs 5.8 +/- 5.2 mm) and fewer clinical end points during follow-up.

Topics: Adolescent; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aorta; Atenolol; Child; Dilatation, Pathologic; Enalapril; Female; Humans; Male; Marfan Syndrome; Propranolol; Prospective Studies; Treatment Outcome

Angiotensin II (AngII) mediates progression of aortic aneurysm, but the relative contribution of its type 1 (AT1) and type 2 (AT2) receptors remains unknown. We show that loss of AT2 expression accelerates the aberrant growth and rupture of the aorta in a mouse model of Marfan syndrome (MFS). The selective AT1 receptor blocker (ARB) losartan abrogated aneurysm progression in the mice; full protection required intact AT2 signaling. The angiotensin-converting enzyme inhibitor (ACEi) enalapril, which limits signaling through both receptors, was less effective. Both drugs attenuated canonical transforming growth factor-β (TGFβ) signaling in the aorta, but losartan uniquely inhibited TGFβ-mediated activation of extracellular signal-regulated kinase (ERK), by allowing continued signaling through AT2. These data highlight the protective nature of AT2 signaling and potentially inform the choice of therapies in MFS and related disorders.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Aortic Aneurysm; Aortic Rupture; Disease Models, Animal; Disease Progression; Enalapril; Losartan; MAP Kinase Signaling System; Marfan Syndrome; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Receptor, Angiotensin, Type 2; Signal Transduction; Transforming Growth Factor beta