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Home > Vascular Annual Meeting > SS27. Loss of STAT1 Is Associated with Increased...

SS27. Loss of STAT1 Is Associated with Increased Aortic Rupture in an Experimental Model of Aortic Dissection

Matthew J. Eagleton, Jun Xu, Brittney Parine, Mingfang Liao, Guy Chisolm, Linda M. Graham
Cleveland Clinic Foundation, Cleveland, OH

OBJECTIVES: Signal transducer and activator of transcription (STAT) 1 has been linked to a variety of pathologic states involved with matrix remodeling, but its role in aortic pathology has not been previously described. The current study hypothesizes that STAT1 regulates aneurysmal degeneration in a mouse model of aortic dissection.

METHODS: Apolipoprotein E knockout mice (ApoE-/-) (n=65) or ApoE/STAT1 (n=25) double knockout mice (ApoE/STAT1-/-) were infused with 1000 ng/kg/min of angiotensin II (Ang II). Systolic blood pressure (SBP) was measured in the rodent tail. At sacrifice, aortic diameters and extent of aneurysm formation were measured by digital microscopy. STAT1 and phosphorylated-STAT1 (P-STAT1) protein levels were assessed in ApoE-/- mice at 0, 7, 14, and 28 days (n=8/time point) by ELISA. Histology was performed using H&E and Movat stains. Statistical analyses included chi-square test, T-test, and ANOVA.

RESULTS: Aneurysms occurred in 8%, 50%, and 80% of apoE-/- mice at 7, 14, and 28 days respectively. Total STAT1 levels were not altered during the course of Ang II infusion, but P-STAT1 levels peaked at 7 days with a 1.4-fold increase over baseline (p<0.05). Aneurysms occurred in 0%, 100%, and 100% of apoE/STAT1-/- mice at 3, 5, and 28 days. In mice infused with Ang II for more than 3 days, aortic rupture occurred more frequently in apoE/STAT1-/- mice (53% v. 19%, p<0.05) and at earlier time points (4.0±0.5 vs. 9.2±0.77 days, p<0.05) compared with apoE-/- mice. SBP did not differ between the groups during Ang II infusion. By 28 days, aneurysms were larger in apoE/STAT1-/- mice compared to apoE-/- mice (2.7±0.4 vs. 1.9±0.1 mm, p<0.05), and were more extensive arising at the level of the left subclavian artery and extending to the infrarenal aorta. H&E and Movat stain did not reveal differences in aortic wall structural content at baseline between apoE-/- and apoE/STAT1-/- mice, and both groups demonstrated equal disorganization in the aneurysmal state.

CONCLUSIONS: P-STAT1 is elevated during aneurysm formation and its loss is associated with a higher rate of aortic rupture and more extensive aneurysms in a mouse model of aortic dissection. Further investigation is necessary to determine if these observations are secondary to an underlying aortic wall abnormality or alterations in vessel wall matrix remodeling.

AUTHOR DISCLOSURES: M.J. Eagleton, None; J. Xu, None; B. Parine, None; M. Liao, None; G. Chisolm, None; L.M. Graham, None.