Probing the Role of Mitochondrial Oxidative Stress in Impaired Vascular Function Among Young Adults With Early Life Adversity
University of Iowa
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.
Description
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. ACEs promote cardiovascular morbidity and mortality in a graded, dose-dependent manner1 and are thus a significant, widespread determinant of cardiovascular disease (CVD). In agreement with preclinical evidence,2 we have established that young adults (18-29 y) with prior ACE exposure exhibit impaired vascular endothelial function (VEF)3 as evidenced by reduced flow mediated dilation even in the absence of clinical CVD r…
Eligibility
- Age range
- 18–29 years
- Sex
- All
- Healthy volunteers
- Yes
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 defin…
Interventions
- Dietary SupplementMitoquinone mesylate (MitoQ)
Participants will consume a single 160 mg dose of mitoquinone mesylate, provided in the form of 6, 20 mg capsules, with water.
- Dietary SupplementPlacebo
Participants will consume a single 160 mg dose of microcrystalline cellulose and tapioca (placebo), provided in 20 mg capsules, with water.
Location
- Integrative Laboratory of Applied Physiology and Lifestyle MedicineIowa City, Iowa