Allelic effects on cerebral and carotid artery passive mechanical properties in young, adult, and aged hAPOE3 and hAPOE4 mice
Authors: Souders Leslie , Hulet Ashley , Patel Reema , Gusek Brikena , Vallejo-Elias Johana , Jones Bucky , Jones Carleton , Eckman Delrae 
Published: May 2023

Alzheimer’s disease (AD) is the most common form of dementia and among the leading mortalities in the US. There is growing evidence supporting a connection between AD and cardiovascular disease (CVD). Variant isoforms of apolipoprotein E (APOE) are risk factors for AD and CVD. Compared to the most common APOE isoform, APOE3 (E3), APOE4 (E4) increases AD risk. In order to study APOE-mediated processes, posterior cerebral arteries (PCA) and common carotid arteries (CCA) 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). Our objective was to determine whether the E3 and E4 allele cause different mechanical properties in the absence of extracellular Ca2+ in the PCA and CCA isolated from young (Y, 3-4mo), adult (Ad, 12-15mo), and aged (Ag, 18-22mo), homozygous E3 and E4, male and female mice. We hypothesized that E4 would alter PCA and CCA structure/function when compared to age matched E3 cohorts. 5-8mm segments of PCA and CCA were isolated, cleaned of connective tissue, cannulated, and placed into an arteriograph. Upon equilibration, all vessels were challenged with 60mM [K+] to assess viability. Vessels not responding to 60mM [K+] were discarded. Mechanical characteristics, including lumen diameter (LD), wall thickness (WT), passive distensibility (PD), and stress/strain (S/S) were measured at intraluminal pressures ranging from 10-140mmHg. We observed no statistical differences in LD, PD, or S/S in PCAs and CCAs of Y and Ad, E3 and E4 mice. For LD and WT, Ag E3 was greater than Ag E4 (p<0.05). In contrast, LD in PCAs and CCAs of Ag E3 mice was larger than in Ag E4 mice (p<0.05). We further observed that PD and S/S in CCAs from Ag E3 was greater than in Ag E4 mice (p<0.05), whereas there was no difference in PD and S/S in PCAs isolated from Ag E3 or E4 mice. The WT of PCA in Y E4 was significantly greater than Y E3 mice (p<0.05). In contrast, WT in Ag E3 mice was larger than Ag E4 mice (p<0.05). There was no difference between WT of Ad E3 and E4 mice. The WT of CCAs was significantly greater in Ag E3 vs Ag E4 mice (p<0.05). There is no difference in WT in CCAs from Y (E3 vs E4) or Ad (E3 vs E4) mice. This data indicates aging has minimal effect on mechanical properties in the PCA. In contrast, CCAs in Ag E4 exhibited greater arterial stiffening as indicated by a decrease in their distensibility and leftward shift in S/S, as evidenced by greater stress for given amount of strain observed in PCAs of Ag E4 mice at increased intraluminal pressures. ABRC/ADHS18-205211 (JVE, TBJ, CBJ, DME), Arizona Alzheimer's Consortium (funded by the Arizona Department of Health Services, Contract No. CTR040636) and matching funds from Midwestern University (DME), Biomedical Sciences Program (BG, LJS, DME), Biomedical Sciences Start-up Funds (DME). LJS and ASH equally contributed as first authors. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.