Mesenteric Artery Reactivity in Young APOE3 and APOE4 Mice

Abstract

IntroductionVariant isoforms of apolipoprotein E (APOE) are risk factors for both Alzheimer’s disease (AD) and cardiovascular disease (CVD), with the APOE4 isoform increasing risk compared to the most common isoform, APOE3. Allelotype alters cerebral artery reactivity and cardiac indices in aged animals (ongoing studies in our lab), yet little is known about how allelotype affects systemic circulation. Thus, we hypothesized that APOE allelotype alters mesenteric arteries (MA) in mice. We determined the mechanical characteristics and vascular reactivity of 3rd‐order MA isolated from young (Y, 3 to 4 mo), male and female 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).MethodsMAs were isolated, cleaned of connective tissue, cut into 8mm segments, and cannulated in an arteriograph chamber to assess vascular reactivity via myogenic tone (MT) and phenylephrine (PE)‐induced constriction (1µM). Passive mechanical properties assessed at intraluminal pressures of 10mm Hg to 140mm Hg included lumen diameter, wall thickness, wall tension, stress vs pressure, distensibility and arterial stress/strain. Data were analyzed using two‐way ANOVA and Students t‐test.ResultsMT was greater in E3 mice compared to E4 mice (P<0.001). K+‐ and PE‐induced constriction were similar between E3 mice and E4 mice. Subtle, yet significant changes were observed in passive mechanical properties. Lumen diameter and wall tension was greater in E4 mice compared E3 mice (P<0.01). Wall thickness was greater in E3 mice vs E4 mice (P<0.05). Stress vs pressure was greater in E4 mice vs E3 mice (P<0.05). E4 mice tended to have greater stress vs pressure and distensibility values than E3 mice, but they did not reach statistical significance. Finally, stress vs strain values in MA from E3 mice and E4 mice were similar.Summary/ConclusionsThese data indicate allelotype alters MA vascular reactivity and structural properties. Additional studies are warranted to determine whether these changes in systemic circulation persist with ageing and contribute to altered cerebral and cardiac structure/function observed in ongoing studies in our lab.