Hypertension drives thoracic aortic aneurysm and dissection in male, but not female, Marfan mice.

Abstract

Hypertension is regarded clinically to be a primary risk factor for thoracic aortic disease, yet few studies have examined roles of sustained elevations in blood pressure in mouse models that are genetically predisposed to aortopathy. We quantified and compared effects of chronic blood pressure elevation, achieved using a high salt diet plus induced endothelial dysfunction, on the ascending aorta in age- and sex-matched adult wild-type and Fbn1^C1041G/+ Marfan syndrome mice. Primary findings included that the aorta was more susceptible to disease progression in male Marfan mice than in either female Marfan mice or male and female wild-type mice. Four weeks of induced hypertension resulted in 40% premature mortality in male Marfan mice as well as marked increases in ascending aortic dilatation, wall thickness, and circumferential material stiffness, as well as decreases in axial stretch, elastic energy storage, and wall strength in the surviving male Marfan mice. Given the pre-existing aortic dilatation in the male Marfan aorta before inducing hypertension and lack of aortic dilatation in the female Marfan mice at this age, the present results are consistent with hypertension exacerbating but not initiating structural and functional dysfunctionalities within a vulnerable aorta, which is consistent with a prior computational model that assessed multiple potential contributors to aortopathy.