Allelic modulation of large (second-order) mesenteric artery mechanical properties in adult APOE3 & APOE4 Mice

Previous studies from our lab have demonstrated age-related changes in vascular structure/function in posterior cerebral arteries (PCA) and left common carotid artery (CA) in male and female mice expressing human-APOE targeted replacement of APOE3 (B6.129P2-APOE tm2(APOE*3)Mae N8) and APOE4 (B6.129P2-APOE tm3(APOE*4)Mae N8) (Taconic Labs). Therefore, we hypothesize that similar changes may be observed in the systemic circulation. We isolated second-order mesenteric arteries (MA) from adult (6-month-old) male and female mice expressing APOE3 (n=3) and APOE4 (n=4). Mesenteric artery segments (5-8 mm in length) were rapidly isolated and cannulated on an arteriograph to assess mechanical properties: lumen diameter (LD), wall thickness (WT), wall:lumen ratio (W:L), distensibility, stress, strain, and stress versus strain (SvS) in the presence of Ca 2+ -free Krebs + diltiazem at intraluminal pressures ranging from 10mmHg–140mmHg. Phenylephrine and potassium-induced contractions were assessed in Ca 2+ -containing Krebs at intraluminal pressures ranging from 10-140mmHg. Data were analyzed using two-way ANOVA, Student’s t-test, and analysis of nonlinear fit. Values were considered statistically different at p<0.05. Our preliminary data indicated APOE4 mice had a greater WT and W:L compared to APOE3. Interestingly, there were no significant differences in the remaining passive mechanical properties (LD, distensibility, stress, strain, SvS). In addition, phenylephrine and potassium-induced contractions were similar in the APOE3 and APOE4 mice. This data suggests changes in passive mechanical properties in APOE4 mice which may resemble premature aging. ABRC/ADHS18-205211 (DME, CBJ), 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 (IW, SM, DME), Biomedical Sciences Start-up Funds (DME). This is the full abstract presented at the American Physiology Summit 2024 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.