Evaluation of cardiovascular structure and function in young and aged female APOE3 and APOE4 mice
Authors: Hoxha Brikena , Jones Carleton , Vallejo‐Elias Johana , Powell Jessica , Virden Thomas , Jones T. Bucky , Eckman Delrae M. 
Published: June 2021

Introduction

Alzheimer's disease (AD) is the most common form of dementia in the United State with age and sex being the biggest risk factors. In addition, individuals with cardiovascular disease (CVD) have an increased risk for development of AD. A link between AD and CVD is apolipoprotein E (APOE), a protein that primarily functions to traffic lipids in the body and brain. Individuals with a particular allele of APOE, APOE4, are at increased risk for developing both CVD and AD/dementia. To study the mechanisms of APOE4‐mediated pathogenesis, mouse models were developed that express the normal human APOE3 (hAPOE3) or APOE4 (hAPOE4) in place of the murine APOE. To the best of our knowledge there have been no studies assessing the relationship between carotid artery (CA) function, thoracic aorta (TA) function, and cardiac (C) function in these mice.

Purpose

We hypothesize that female mice expressing hAPOE4 will exhibit augmented age related decline in C, TA and CA function than aged matched hAPOE3 mice.

Methods

In vivo investigation of C, TA ad CA structure/function was assessed in young (4±1months) and aged (18±2 months) female hAPOE3 and hAPOE4 mice using high‐resolution ultrasound (U/S). In addition, blood pressure (BP) was determined using the tail‐cuff method. All U/S and BP values were collected under isoflurane anaesthesia. Results were considered significant at p<0.05.

Results

hAPOE3 mice exhibited an age‐related increase in bodyweight (p<0.05) and hAPOE3 mice weighed significantly more than hAPOE4 mice at 18–20 months (p<0.05). There was no age‐associated increase in bodyweight in the hAPOE4 mice. CA structure and function was assessed by wall thickness (WT) and pulse wave velocity (PWV) respectively. Both hAPOE3 and hAPOE4 mice displayed an age‐related increase in WT (p<0.05). CA PWV was significantly greater in aged hAPOE4 vs young APOE4 mice (p<0.05), however there was no age‐related CA PWV increase in hAPOE3 mice. Both hAPOE3 and hAPOE4 mice exhibited an age‐related increase in TA PWV (P<0.05), but measurements of aortic structures: aortic annulus, sinus of valsalva, and sinotubular junction, showed no significant age‐related changes. Cardiac output (CO) and stroke volume (SV) was higher in young‐ and aged‐ hAPOE3 mice compared to age matched hAPOE4 mice (CO: p<0.05 and SV: p<0.05). All other cardiac indices (e.g., stroke volume, ejection fraction, E/A ratio, etc.) were similar between groups. Finally, the systolic and diastolic BP values showed no significance difference between groups.

Summary/Conclusion

These preliminary data suggest that female hAPOE3 and APOE4 mice exhibit age‐related changes in C, TA and CA structure and function. Additional studies will be needed to determine whether hAPOE mice exhibit structural and/or functional changes similar to that seen in women.

Support or Funding Information

Midwestern University/Arizona Alzheimer's Consortium (DME, CJ, JVE, JP, TV, BJ), Biomedical Sciences start‐up funds (DME).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.