(719.9) Early Life Stress and Heart Function in the Pristane-Induced Model of Systemic Lupus Erythematosus (SLE) in Mice

Poster Board Number: E139

Felix Cruz-Ojeda (University of Alabama at Birmingham), Cailin Kellum (University of Alabama at Birmingham), Lihao He (University of Alabama at Birmingham), Min Xie (University of Alabama at Birmingham), Jennifer Pollock (University of Alabama at Birmingham)

Early life stress (ELS) is defined as childhood adversity such as maltreatment (e.g., verbal and physical abuse), sexual abuse, and household dysfunction occurring prior to age 18. ELS is associated with increased risk of chronic disease and poorer health outcomes earlier in adulthood compared to those without exposure to ELS. SLE is an autoimmune disease most prevalent in women with high mortality from cardiovascular disease and influenced by environmental factors including psychosocial stress such as ELS. SLE affects multiple organs including the heart. Pericarditis and heart failure are known pathologies affecting SLE patients at a higher rate than patients without SLE, however the influence of ELS on heart disease development is unknown. We hypothesized that a mouse model of ELS, maternal separation with early weaning, MSEW, have increased risk of heart disease particularly in response to the development of SLE in adulthood. MSEW entails separating pups from the dam 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. The pristane-induced model of SLE uses a single intraperitoneal (i.p.) injection to induce SLE-like symptoms in female mice. Previous data have shown that Anti-Smith autoantibody is not elevated in the SLE animals at 5 months after the i.p. injection compared to the NR and MSEW controls (P=0.0514). However, there is an increase in the presence of Anti-Smith autoantibody in the SLE animals at 6 months after the i.p. injection (P=0.0007). Therefore, our objective was to determine parameters of systolic and diastolic heart function in NR control mice (NR+CON), NR+SLE, MSEW, and MSEW+SLE at time points early in the development of SLE at 4 months post-injection with a VEVO 3100 high resolution echocardiography. Systolic function assessed by Ejection Fraction (P=0.3535), Fractional Shortening (P=0.3301), Left ventricular Mass (P=0.9216), Left Ventricular Diastolic Volume (P=0.4767), and Left Ventricular Systolic Volume (P=0.9568) showed no significant differences. Similarly, diastolic function assessed by E/e’ ratio (P=0.9159), Myocardial Performance Index (P=0.2867), MV E/A ratio (P=0.9231), and e’/a’ ratio (P=0.1104) showed no significant differences. These results suggest that the pristane-induced model of SLE or ELS did not induce systolic or diastolic dysfunction early in the development of SLE. Future work will focus on a longitudinal strategy for the identification of heart dysfunction in mice with SLE.

Funding: K01-DK-105038 KAH, RO1 HL 136936 JSP and DPM. NIH T32 DK 116672.
University of Alabama at Birmingham PostBaccalaureate Research Education Program (PREP).