Characterization of Aortic Function and Structure in the Human Apolipoprotein E Mouse Model
Authors: Dickman Raechel , Talley Nicholas , Hoxha Brikena , Alexander Tia , Curry Tala , Johnson Nathan , Gadagkar Sudhindra , Vallejo‐Elias Johana , Jones T. Buckey , Esfandiarei Mitra 
Published: June 2021

Apolipoprotein E (APOE) is a multifunctional protein with three isoforms (e2, e3, and e4) that correspond with diverse functional and pathological manifestations. Most notably, the e4 allele has been associated with an increased risk of cardiovascular disease, and is considered a prominent risk factor for the development of late onset Alzheimer disease (AD). AD is a progressive neurodegenerative disease and the leading cause of dementia. Although research in AD has been ongoing, the pathogenesis of the disease remains elusive. The discovery of cerebral vascular abnormalities in AD patients and the association of ApoE e4 (APOE4) with cardiovascular disease has led to the hypothesis that the condition may initially arise from peripheral vascular dysfunction. However, little is known about the pathological consequences associated with the apolipoprotein isoforms in major peripheral arteries, such as the aorta.

In this study, we aimed to characterize the functional (vasoconstriction and vasodilation) and structural (aortic wall elasticity and integrity) characteristics of the thoracic aorta in wild type C57BL/6, targeted replacement APOE3, and targeted replacement APOE4 mice, at 12 and 18 months of age, using small chamber myography. In order to determine early changes that may be associated with vascular abnormalities noted at older ages, we aimed to evaluate cardiac and aortic function and structure including aortic root diameter, aortic stiffness, and cardiac parameters in young mice of all experimental groups using high‐resolution, high‐frequency ultrasound imaging. Our data showed a significant increase in phenylephrine (PE)‐induced contraction in aortic segments isolated from 12 and 18‐month old APOE4 mice as compared to APOE3 mice. There was no evident difference in acetylcholine‐induced relaxation between experimental groups at 12 or 18 months of age. However, the rupture point was significantly reduced in aortic segments isolated from APOE4 mice when compared to wild type mice, indicating a decrease in aortic wall integrity in APOE4 mice. Aortic root diameter at the sinotubular junction was significantly increased in APOE4 mice when compared to APOE3 mice, but was not significant at the regions of aortic anulus or sinus of Valsalva. Pulse wave velocity, a reliable index of aortic wall stiffness, was comparable amongst genotypes at 3 months of age. Cardiac stroke volume was significantly increased in APOE4 mice when compared to wild type, and there was a decreasing trend in left ventricular mass between wildtype, APOE3, and APOE4 mice. This study provides the first preliminary evidence of peripheral vascular dysfunction in the well‐established mouse model of AD (APOE).

Support or Funding Information

This study was funded by a Midwestern University graduate fund.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.