Probing the Role of Mitochondrial Oxidative Stress in Impaired Vascular Function Among Young Adults With Early Life Adversity
Trial Parameters
Brief Summary
Adverse childhood experiences (ACEs) represent highly stressful events in the first 18 years of life that include abuse, neglect, and household and community-level dysfunction. Greater exposure to ACEs are associated with greater increases in the risk of cardiovascular diseases and death. Our laboratory has previously observed that vascular function is disrupted in young adults with prior ACE exposure, even though these individuals appear to be healthy clinically (i.e., no classic clinical cardiovascular disease risk factors). There is a need to identify and understand the biological mechanisms underlying these vascular impairments to inform effective interventions to reduce cardiovascular risks the millions of individuals affected by ACEs. The body's response to stress is coordinated across various systems, all of which depend on energy supplied by mitochondria (often referred to as the "powerhouse of cells"). Based on new evidence across multiple physiological systems from our team, our overarching hypothesis is that disruption of mitochondrial function contributes to cardiovascular impairments among young adults with ACEs. Here we propose the initial pilot work necessary to begin to understand these associations, which will directly inform identification of individuals who may be most vulnerable to stress-related cardiovascular risk and the development of interventions to promote cardiovascular-stress resilience. Our aims are to: 1. Determine whether mitochondrial oxidative stress contributes to impaired vascular function among young adults who experienced early life adversity. 2. Determine whether reducing mitochondrial oxidative stress improves the cellular stress and integrated cardiovascular response to laboratory-based psychosocial stress among young adults who experienced early life adversity.
Eligibility Criteria
Inclusion Criteria: * 18-29 years * ACE score \>=4 Exclusion Criteria: * Resting arterial blood pressure \>140/90 mmHg * BMI \<=17 or \>= 35 * Are on a weight-loss diet or involved in a formal weight-loss program or are not intentionally weight stable for 6 months (+/- 5 kg) prior to the study. * Cardiovascular or metabolic prescription drug use * Vasoactive antidepressant drug use (SSRIs and clonidine) * Current heavy alcohol use, as defined as binge drinking on 5 or more days in the last month, or consuming more than 7 (women) or 14 (men) drinks per week in the last month (per NIAAA definition) * Current or recent (within the last 6 mo.) illicit drug use disorder as indicated by a score of 3 or greater on the Drug Abuse Screening Test (DAST-10) * Current tobacco or nicotine use * Vaping * Regular vigorous (\>6 METs) aerobic exercise (\>4 bouts/week, \>30 min/bout) * dietary supplementation with antioxidants or habitual use of NSAIDs * Currently pregnant or breastfeeding