Mice expressing human apolipoprotein E4e exhibit altered thoracic ascending aortic elastic properties

Abstract

Alzheimer's disease (AD) is characterized with the progressive loss of cognitive abilities that typically presents in the elderly population, therefore most research has focused primarily on the brain. Hypertension, obesity and atherosclerosis are often comorbidities that present with AD patients. Per the American Heart Association, by 2035 nearly half of the US population will suffer from some type of vascular disease. Despite that, peripheral vascular dysfunction within the progression of AD has not been studied in detail. Apolipoprotein‐ɛ (ApoE) is a lipid‐binding protein that is a major factor in cholesterol metabolism in the brain and periphery. ApoE is polymorphic and the expression of the ApoE4 allele is associated with late onset AD. Conversely, the ApoE3 allele has been shown to likely prevent neurodegeneration, suggesting a protective role for ApoE3 protein in the brain. In this study we investigated the functional (vasoconstriction & vasodilation) and structural (elastin fiber organization and elasticity) properties of the aorta in 18‐month old mice expressing human ApoE4 or ApoE3, and wild type C57BL/6 mice using wire myography and conventional histological staining. Our data shows that phenylephrine‐induced contraction and acetylcholine‐induced vasodilation is not different among experimental groups. However, elastin fiber fragmentation and disorganization were observed within the aortic wall in ApoE4 mice as compared to age‐ and sex‐matched ApoE3 and C57BL/6 mice. Furthermore, the stretch‐induced wall stress and reversibility of elasticity were significantly reduced in aortic segments isolated from ApoE4 mice indicating an increase in aortic wall stiffness in ApoE4 mice. These data present the first evidence that neurodegenerative pathology in ApoE4 mice is associated with pathologic changes in the aortic wall that leads to increased vascular wall stiffness and reduced elasticity. This will establish a new direction aimed at studying the relationship between observed brain pathology in AD and abnormal changes in peripheral vascular function and structure that occur in a relevant mouse model for the disease.Support or Funding InformationThis study is supported by funding from Midwestern University Alzheimer's Advisory Committee.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.