Cardiovascular characterization of young and aged, female and male APOE4 mice

Abstract

IntroductionAlzheimer'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. CVD remains the leading killer of both women and men in the United States. By the age of 65, women have 1 in 6 chance of developing AD compared to a 1 in 11 chance for men. Therefore, out of the 5 million people living with Alzheimer's in the U.S., 3.2 million are women. Because of these differences, this study was designed to assess the effect of the hAPOE4 genotype on carotid artery (CA) function, thoracic aorta (TA) function, and cardiac (C) function in young and aged hAPOE4.PurposeWe hypothesize that female mice expressing hAPOE4 will exhibit augmented age related decline in C, TA and CA function than aged matched male hAPOE4 mice.MethodsIn vivo investigation of C, TA ad CA structure/function was assessed in young (4±1months) and aged (18±2 months), female and male, hAPOE4 mice using high ‐ resolution ultrasound (U/S) system. 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.ResultsIn this study, young and old, female and male hAPOE4 mice exhibited similar bodyweights. CA structure and function was assessed by wall thickness (WT) and pulse wave velocity (PWV) respectively. Both female and male hAPOE4 mice displayed an age‐related increase in PWV (p<0.05), but only the female APOE4 mice displayed an age related increase in CA wall thickness (WT) (p<0.05). Female and male 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 sex or age related change. Interestingly, except for a modest increase in mitral valve deceleration time with age in male hAPOE4 mice, there was no effect of age or sex on cardiac parameters assessed by U/S (e.g., cardiac output, ejection fraction, stroke volume, etc.). Finally, blood pressures were similar in female and male, young and old hAPOE4 mice with the only exception being an elevated pulse pressure in young male hAPOE4 mice vs young female APOE4 mice (p<0.05).Summary/ConclusionThese preliminary data suggest that female and male, hAPOE4 mice, exhibit age‐related changes in TA and CA structure and function. Additional studies will be needed to determine whether hAPOE4 mice exhibit structural and/or functional changes similar to that seen in women and men.Support or Funding InformationMidwestern University/Arizona Alzheimer's Consortium (DME, JVE, CJ, 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.