Abstract Body: Early life stress (ELS), or adverse experiences occurring before the age of 18, significantly increase the risk of developing cardiovascular disease later in life. These adverse experiences are alarmingly common and the CDC estimates that 1.9 million cases of CVD could be prevented without ELS. We previously found increased aortic stiffness as well as increased histone deacetylase (HDAC) activity in a mouse ELS or maternal separation with early weaning (MSEW). We hypothesized that a pharmacologic inhibition of class IIa HDAC activity will reduce aortic stiffness and cardiovascular risk in a mouse model of ELS. Mice underwent the MSEW model of early life neglect where pups were separated from the dams for 4 hours/day from postnatal days (PD) 2-5 then 8 hours/day for PD 6-16 then weaned early at PD 17. Normally reared (NR) control litters remained undisturbed with dam and were weaned at a normal age of PD 21. At 10 weeks of age, pre-treatment pulse wave velocity (PWV) was performed on MSEW and NR male and female mice. Mice were then treated with class IIa HDAC inhibitor MC1568 or vehicle carboxymethylcellulose (CMC) via intraperitoneal injection (15mg/kg) twice/week for 2 weeks. Post-treatment PWV was recorded at 12 weeks of age in male and female mice. By 2-way ANOVA, male MSEW mice show elevated PWV as compared to NR pre-treatment controls (mm/sec; NR male: 1.53+0.06, MSEW male: 2.16+0.06 n=6, p=<0.0001). MC1568 treatment ameliorated the PWV phenotype in MSEW (p=0.0005) with no change in NR controls (mm/sec, post-MC1568; NR male: 1.71+0.02, MSEW male: 1.68+0.09; n=6, Interaction p=0.0007, F(1,10)=23). Females followed a similar trend (mm/sec pre-treatment: NR female: 1.62+0.05; MSEW female: 2.19+0.18; n=3. Post-treatment: NR female: 1.48+0.11; MSEW female: 1.65+0.16 n=3,2). Flow cytometry on the blood of the female mice demonstrated elevated inflammatory monocytes (CD11b⁺/Ly6c^high) in MSEW mice treated with vehicle as compared to NR. This elevation was ameliorated in the MC1568 treated group (%CD45; MSEW vehicle: 25.29+1.8, NR vehicle: 19.2+3.5, MSEW MC1568: 9.25+2.12, NR MC1568: 16.35+2.4; N=3,3,2,3). These findings suggest a key role of class IIa HDAC activity in mediating cardiovascular risk following ELS. Future studies aim to further investigate the pathways by which class IIa HDACs mediate vascular stiffness and immune activation in ELS.