Abstract 352: Locally Deployed Perivalvular Leptin Promotes Thickening of Aortic Valve Leaflets Associated with Remodeling of the Left Ventricle in ApoE-Deficient Mice
Background: Locally available leptin is involved in atherogenesis and remodeling of the arterial wall. Recently, we demonstrated its contribution to aortic aneurysm formation in mice, and hypothesized that leptin may also drive the process of aortic valve stenosis (AVS) by promoting medial degeneration in the valve cusps.
Methods: ApoE-deficient mice underwent left mini-thoracotomy to allow the deployment of a miniature polyglycolic-base film designed for sustained release of mouse leptin (20μg), or placebo film on the aortic surface at the peri-valvular region. All mice received a high fat diet, and underwent serial cardiac echo examinations thereby, recording the diameter of the ascending aorta, blood flow through the aortic valve, and left ventricle morphology, throughout 45 days’ follow up.
Results: Longitudinal echocardiography assessment in leptin vs placebo treated mice revealed progressive dilatation of the proximal ascending aorta, corroborating postmortem histological evidence for local fragmentation of elastic lamellas, and depletion of smooth muscle cells in the aortic wall. Leptin receivers manifested increased aortic valve leaflets’ thickening (p=0.05). This was associated with local proliferation α-SMA and TGF-β positive cells, suggestive of valve interstitial cells (VICs). Leaflets’ thickening correlated with in vivo echocardiography data indicating increased peak systolic velocity across the aortic valve (p=0.02). Also, increased left ventricle wall thickening (p=0.05), and decreased ventricular cross section area (p=0.01) were evident in leptin receiving mice.
Conclusions: These preliminary results indicate that peri-aortic, peri-valvular leptin application, simulating local leptin synthesis, promotes remodeling of the aortic valve in ApoE-deficient mice, by unknown mechanisms. Leaflet thickening is associated with remodeling of the left ventricle, thus simulating and potentially providing a model for AVS pathogenesis and secondary effects.
Author Disclosures: D. Ben Zvi: None. S. Fisch: None. K.C. Ozaki: None. F.J. Schoen: None. J. Schneiderman: None.
- © 2014 by American Heart Association, Inc.