Abstract 2607: TGF-beta 1 as a Diagnostic Biomarker for Acute Aortic Dissection Type A in a Mouse Model of Marfan Syndrome

Abstract

Objectives: Acute aortic dissection type A is the main cause of mortality in patients with Marfan Syndrome (MFS). The aim of this study was to develop a procedure to surgically induce an acute aortic dissection type A in a mouse model of MFS, and to discover a diagnostic biomarker of the aortic lesion. Methods: Ten fibrillin-1 deficient (Fbn1C1039G/+) and ten wild-type (WT) mice at 8 months of age were intubated, ventilated and the aorta exposed via hemisternotomy. We hypothesized that an aortic dissection type A could be induced by performing an aortic clamp injury. Serum samples were collected before and after induction (30 min) of the aortic lesion from the right femoral vein. Total (acid activated) TGF-beta 1 concentrations were measured by ELISA. Echo measurements of the aortic root were obtained from a parasternal long axis view in all mice. Results: Transthoracic echocardiography of the aortic root performed prior to surgery showed significantly larger diameters in Fbn1C1039G/+ mice compared to WT (p<0.0001). Aortic clamp injury led in Fbn1C1039G/+ and WT mice to a reproducible aortic wall hematoma, and intimal tears. Hematoxylin-eosin stained histological sections revealed aortic dissection of the medial layer in Fbn1C1039G/+ mice but not in WT (p<0.001). Elastin-stained sections revealed a significantly higher elastic fiber fragmentation and disarray in Fbn1C1039G/+ aortas compared to WT (p<0.001). Aortic dissection in Fbn1C1039G/+ mice was limited to the ascending aorta. Mean TGF-beta 1 serum concentrations significantly increased after inducing the aortic lesion in Fbn1C1039G/+ mice (p=0.01; 130 ng/ml vs 412.9 ng/ml) but not in WT mice (p=0.2). Sham operated Fbn1C1039G/+ and WT mice showed no difference in TGF-beta 1 serum concentrations before and after surgery (p=0.7; n=4). Conclusions: We present a reproducible and in the short-term non-lethal mouse model of a surgically induced acute aortic dissection type A in MFS. TGF-beta 1 serum concentrations after inducing the aortic lesion significantly increased in Fbn1C1039G/+ mice but not in WT and Sham operated mice. TGF-beta 1 is a promising diagnostic biomarker for an acute aortic dissection type A in MFS.