Childhood psychosocial stress is linked with impaired vascular endothelial function, lower SIRT1, and oxidative stress in young adulthood

Our study provides novel evidence that young adult women with moderate-to-severe adverse childhood experience (ACE) exposure present impaired endothelial function and lower circulating sirtuin 1 (SIRT1) concentrations than age-matched controls. However, an 8-wk exercise intervention was unable to augment endothelial function or SIRT1 concentrations in a subset of those with ACEs. Our data suggest that ACEs-related impairments in endothelial function may be secondary to decreased NO bioavailability via SIRT1 and/or oxidative stress-related mechanisms. Adverse childhood experiences (ACEs) are psychosocial stressors that occur during sensitive developmental windows and are associated with increased lifetime cardiovascular disease (CVD) risk in a dose-dependent manner. Vascular endothelial dysfunction is a pathophysiological mechanism that promotes hypertension and CVD and may be a mechanism by which ACEs contribute to lifetime CVD risk. We examined whether exposure to ACEs is associated with reduced vascular endothelial function (VEF) in otherwise healthy, young adult women (20.7 ± 3 yr) with (ACE + ) versus without (ACE − ) ACEs, explored whether differences in circulating sirtuin 1 (SIRT1) or systemic oxidative stress could explain ACEs-related differences in VEF, and examined the ability of a pilot, 8-wk exercise intervention to augment VEF and SIRT1 or reduce oxidized LDL cholesterol (oxLDL) in ACE + young adult women. Forty-two otherwise healthy young adults completed this study. Prior to the intervention, VEF ( P = 0.002) and SIRT1 ( P = 0.004) were lower in the ACE + than ACE − group, but oxLDL concentrations were not different ( P = 0.77). There were also significant relationships ( P ≤ 0.04) among flow-mediated dilation (FMD), SIRT1, and oxLDL in the ACE + , but not ACE − group. Adjusting for circulating SIRT1 and oxLDL reduced the differences in FMD observed between groups ( P = 0.10), but only SIRT1 was a significant adjuster of the means ( P < 0.05). Finally, the exercise intervention employed was unable to enhance VEF or SIRT1 in the ACE + exercise group. Our data suggest that ACEs likely increase susceptibility to hypertension and CVD by causing endothelial dysfunction, perhaps through a SIRT1 pathway-related mechanism. NEW & NOTEWORTHY Our study provides novel evidence that young adult women with moderate-to-severe adverse childhood experience (ACE) exposure present impaired endothelial function and lower circulating sirtuin 1 (SIRT1) concentra