Abstract
Aortic aneurysm refers to dilatation of the aorta due to loss of elasticity and degenerative weakening of its wall. A preventive role for osteoprotegerin (Opg) in the development of abdominal aortic aneurysm has been reported in the CaCl2-induced aneurysm model, whereas Opg was found to promote suprarenal aortic aneurysm in the AngII-induced ApoE knockout mouse aneurysm model. To determine whether there is a common underlying mechanism to explain the impact of Opg deficiency on the vascular structure of the two aneurysm models, we analyzed suprarenal aortic tissue of 6-month-old ApoE-/-Opg-/- mice after AngII infusion for 28 days. Less aortic dissection and aortic lumen dilatation, more adventitial thickening, and higher expression of collagen I and Trail were observed in ApoE-/-Opg-/- mice relative to ApoE-/-Opg+/+ mice. An accumulation of α-smooth muscle actin and vimentin double-positive myofibroblasts was noted in the thickened adventitia of ApoE-/-Opg-/- mice. Our results suggest that fibrotic remodeling of the aorta induced by myofibroblast accumulation might be an important pathological event which tends to limit AngII-induced aortic dilatation in ApoE -/-Opg-/- mice.
Highlights
Aortic aneurysm (AA) refers to a dilatation of the aorta due to loss of elasticity and degenerative weakening of its wall
Consistent with results reported by Moran et al [19], we found that Opg deficiency tended to limit AngII-induced aortic dissection and dilatation
We observed adventitial thickening accompanied by myofibroblast accumulation and increased expression of collagen I and TNF-related apoptosis-inducing ligand (Trail) in aneurysm tissue of ApoE-/-Opg-/- mice
Summary
Aortic aneurysm (AA) refers to a dilatation of the aorta due to loss of elasticity and degenerative weakening of its wall. Continuous expansion of the aorta results in rupture and is associated with a high mortality rate [1]. Analyses of AA in experimental animal models, including the CaCl2-induced mouse model and the AngII-induced ApoE knockout (KO) mouse model [2, 3], are important for understanding the pathogenesis of this disease and for developing effective drug treatments aimed at arresting aortic expansion [4,5,6,7]. Osteoprotegerin (Opg, referred to as TNFRSF11B), a member of the tumor necrosis factor (TNF) receptor superfamily, functions as a decoy receptor to regulate various factors.
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