Abstract P081: Early Life Stress (ELS) Induces Greater Aortic Pulse Wave Velocity (PWV) Through Reactive Oxygen Species (ROS)

Abstract

ELS, such as verbal and physical abuse or maltreatment, is linked to a greater risk ofcardiovascular disease (CVD) in adulthood. Aortic stiffness, an independent predictor of CVD,has been suggested as a prognostic tool for early detection and intervention in at-riskpopulations. Several human studies have shown that aortic stiffness (assessed by PWV) isincreased in both adults and adolescents with ELS. ELS mouse models, such as maternalseparation with early weaning (MSEW), show aortic endothelial dysfunction with increasedsuperoxide and systemic inflammation, which are both present in humans with ELS exposureand contribute to aortic stiffness. We hypothesized that MSEW mice develop aortic stiffness in aROS-dependent manner at an early age. The MSEW protocol entails separating pups from thedam 4h/day (postnatal, PD 2 to 5) and 8h/day (PD 6 to 16) followed by weaning at PD17.Normally-reared (NR) litters remain with the dam and are weaned at PD21. Female and maleMSEW and NR mice were treated for 2 weeks with the ROS scavenger, TEMPOL (30mg/kg/day; drinking water) from 8 weeks of age. PWV was assessed prior to and after TEMPOLtreatment. PWV was significantly increased in MSEW mice at baseline (NR: 1.95 mm/sec ±0.15, MSEW: 2.60 mm/sec ± 0.17, p=0.009) in both sexes similarly. PWV was not significantlydifferent between MSEW and NR mice after TEMPOL treatment (NR: 1.78 mm/sec ± 0.06,MSEW: 1.97 mm/sec ± 0.12, p<0.05). MSEW mice had significantly more aorticCD11b + Ly6C + CX3CR1 + inflammatory monocytes compared to NR mice (NR: .9% ± 0.31,MSEW 1.5% ± 0.25, p=0.014) at baseline, however TEMPOL did not affect this. TEMPOLtreatment significantly decreased CD11b + F4/80 + MHCII hi inflammatory resident macrophages inMSEW mice compared to NR mice (Median Fluorescent Intensity; NR: 1,235,274 ± 54413,MSEW : 944,446 ±11728, p=0.007). In conclusion, ELS induces increased aortic stiffness in aROS-specific manner at an early age. Inflammatory resident macrophages may contribute to theELS-specific ROS-dependent mechanism. The mechanisms identified in this work arepotentially powerful tools for preventative therapeutics to reduce CVD burden in ELS-populations.