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.
18-29 years
ACE score >=4
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
Parallel
Mitoquinone mesylate (MitoQ)
Dietary supplementParticipants will consume a single 160 mg dose of mitoquinone mesylate, provided in the form of 6, 20 mg capsules, with water.
Placebo
Dietary supplementParticipants will consume a single 160 mg dose of microcrystalline cellulose and tapioca (placebo), provided in 20 mg capsules, with water.
Vascular endothelial function
Vascular endothelial function will be assessed using the brachial artery flow mediated dilation technique
Blood pressure
The blood pressure response to psychosocial stress induced by the Trier Social Stress Test will be determined using beat-to-beat blood pressure measurement by finger photoplethysmography (or brachial artery blood pressure in the case of equipment errors). The Trier Social Stress Test will be performed after post-supplementation measurement of vascular endothelial function (FMD).
Endothelial Cell Microparticle Release
Endothelial cell microparticle release will be quantified from platelet-poor plasma in response to psychosocial stress induced by the Trier Social Stress Test. The Trier Social Stress Test will be performed after post-supplementation measurement of vascular endothelial function (FMD).
Cortisol
Cortisol will be quantified from drool collected passively to assess the HPA-axis response to psychosocial stress induced by the Trier Social Stress Test. The Trier Social Stress Test will be performed after post-supplementation measurement of vascular endothelial function (FMD).
Total Peripheral Resistance
The total peripheral resistance response to psychosocial stress induced by the Trier Social Stress Test will be determined using beat-to-beat blood pressure measurement by finger photoplethysmography. The Trier Social Stress Test will be performed after post-supplementation measurement of vascular endothelial function (FMD).
Cardiac Output
The cardiac output response to psychosocial stress induced by the Trier Social Stress Test will be determined using beat-to-beat blood pressure measurement by finger photoplethysmography using ModelFlow. The Trier Social Stress Test will be performed after post-supplementation measurement of vascular endothelial function (FMD).
Growth Differentiation Factor 15
Induction of GDF-15 will be quantified from plasma in response to psychosocial stress induced by the Trier Social Stress Test. The Trier Social Stress Test will be performed after post-supplementation measurement of vascular endothelial function (FMD).
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University of Iowa
Lead sponsor
MitoQ Limited
Collaborator
