Cerebral Artery Reactivity in Adult APOE3 and APOE4 Mice
Authors: Patel Reema G. , Hoxha Brikena , Ion Elena , Vallejo‐Elias Johana , Jones Carleton “Buck” , Powell Jessica , Virden Thomas , Struthers Jason , Jones T. Bucky , Eckman Delrae M. 
Published: June 2021

Introduction

Alzheimer's disease (AD) is the most common form of dementia, and is the 6th leading cause of death in the US. Growing evidence supports a link between AD and cardiovascular disease (CVD). Variant isoforms of apolipoprotein E (APOE) are risk factors for both AD and CVD. The most common APOE isoform, APOE3, has neutral risk for developing AD, whereas APOE4 increases AD risk. In order to study APOE‐mediated processes, cerebral vessels were isolated from mice expressing human‐ApoE targeted replacement of APOE3 (B6.129P2‐Apoetm2(APOE*3)Mae N8) and APOE4 (B6.129P2‐Apoetm3(APOE*4)Mae N8)(Taconic Labs).

Objective/Hypothesis

Our objective was to characterize vascular function by assessing myogenic tone (MT) and mechanical characteristics in the posterior cerebral artery (PCA) isolated from APOE3 and APOE4, male and female mice. We hypothesize that APOE4 expression in female mice alters vascular smooth muscle function, leading to vascular remodeling and altered cerebrovascular structure/function in PCAs compared to PCAs isolated from age matched control (APOE3) mice.

Methods

PCAs were rapidly isolated from adult (12 month), male and female, APOE3 and APOE4 mice, cleaned of connective tissue, cut into 5 mm segments, and cannulated in an arteriograph chamber to assess mechanical characteristics and myogenic tone (MT). Upon equilibration, vessels were challenged with 60 mM [K+]o at an intraluminal pressure of 60 mm Hg. Vessels not responding to elevated [K+]o were not used in the study. Active/passive wall tension, wall thickness, distensibility, stress/strain and MT was measured with step‐wise increases in intraluminal pressure (10 mm Hg to 140 mm Hg).

Results

PCAs from female APOE3 mice showed greater MT than PCAs from male APOE3 mice (P<0.05). In addition, female APOE4 mice showed greater MT than male APOE4 mice (P<0.05). When challenged with 60 mM [K+]o, all groups showed similar % constriction. Passive wall tension was lower in female APOE4 compared to male APOE4 mice (P<0.05). Male APOE4 mice showed greater wall thickness than female APOE4 mice and male APOE3 mice (P<0.05). Preliminary data suggests a difference in distensibility between male and female APOE4 mice but no differences in stress/strain throughout the groups.

Summary/Conclusions

Our data suggests PCA structure and function are altered in APOE4 mice compared to age matched APOE3 mice. Increased MT in female APOE3 and APOE4 mice compared to males indicates sex differences in the PCA's. Elevated MT observed in APOE4 female mice may be a result of vascular remodeling. Our data suggests differences in mechanical characteristics between male and female APOE3 and APOE4 mice. We continue to collect data to better understand these differences.

Support or Funding Information

Funding: ABRC/ADHS18‐205211 (DME, JVE, CJ, JP, TV, TBJ), Biomedical Sciences Program (RP, DME), Biomedical Sciences Start‐up Funds (DME)

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