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

Abstract

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 years) with (ACE+) versus without (ACE-) ACEs, explored whether differences in circulating SIRT1 or systemic oxidative stress could explain ACEs-related differences in VEF, and examined the ability of a pilot, 8-week 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 associations (P ≤ 0.04) among 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). 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 via reduced vascular function, perhaps through a SIRT1 pathway-related mechanism.

The Link Between Childhood Adversity and Cardiovascular Disease Risk: Role of Cerebral and Systemic Vasculature

“… 46 Similar outcomes have been recently confirmed in young adults exposed to ACEs with comparable associations identified between macrovascular function and the reported number of ACEs. 9 Current results extend previous findings and identify that individuals who experienced adversity during childhood also present with a significantly diminished vascular endothelial function both in the macro- and the micro-vasculature. Endothelial cells, and therefore endothelial dysfunction, differ in structure and phenotype, depending on the vessel type, and macro and microvessels respond differently to insults.…”

“… 3–5 Vascular endothelial dysfunction, a well-established precursor of CVD, 6 is an important mediator in the ACE-induced increase in CVD risk. 7 Prevailing data in the literature supports that young adults exposed to ACE exhibit greater peripheral vascular resistance, augmented arterial stiffness, and reduced endothelial function, 8 , 9 all independent predictors of CVD events.…”

How do Adverse Childhood Experiences get Under the Skin to Promote Cardiovascular Disease? A Focus on Vascular Health

“…Initial evidence regarding the pathophysiological mechanisms by which ACEs promote CVD largely emerged from pre-clinical, mouse models of early life stress, such as maternal separation with early weaning 4 . Recently, Jenkins et al 5 translated the preclinical evidence on ACEs and vascular function to young adults. Specifically, young adult women (∼20 years old) with moderate-to-severe (≥4) ACE exposure exhibited endothelial dysfunction, as measured by the flow mediated-dilation (FMD) technique.…”

“…Similarly, Jenkins et al also found that vascular dysfunction was present in those with ACEs without deviations in traditional risk factors. 5 While ACEs are associated with increased likelihood of risky health behaviors, it appears that the association between ACEs and CVD may be independent of certain risky behaviors. For example, Jenkins et al 5 excluded individuals who smoked or used illicit drugs, and the ACEs cohort was matched to the control group for physical activity status.…”

“… 5 While ACEs are associated with increased likelihood of risky health behaviors, it appears that the association between ACEs and CVD may be independent of certain risky behaviors. For example, Jenkins et al 5 excluded individuals who smoked or used illicit drugs, and the ACEs cohort was matched to the control group for physical activity status. The Georgia Heart and Stress Study demonstrated an association between ACE exposure and increased systolic and diastolic blood pressure (that becomes apparent in late young adulthood (34 – 38 years)) that persisted after adjustment for physical activity, smoking, and illicit drug use.…”