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

Am J Physiol Heart Circ Physiol. 2021 Sep 1;321(3):H532-H541. doi: 10.1152/ajpheart.00123.2021. Epub 2021 Jul 30.

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 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) 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.

Keywords: adversity; early life stress; flow-mediated dilation; social determinants of health; vascular function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Adverse Childhood Experiences*
  • Aged
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress*
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Stress, Psychological / etiology
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology

Substances

  • SIRT1 protein, human
  • Sirtuin 1