Study of the Effects of Negative Emotions on Endothelial Function

Atherosclerosis-related cardiovascular disease (CVD) events remain the leading causes of
morbidity and mortality in industrialized nations. Atherosclerosis is a diffuse disease
characterized by the deposition of lipid and other blood-borne material within the arterial
wall. Evidence demonstrates that disruption of an arterial atherosclerotic plaque and
subsequent thrombus formation is responsible for the onset of CVD events. Cardiovascular
research efforts have been directed toward the identification of early underlying factors
that initiate this cascade.

It has been known for some time that the experience of negative emotions is associated with
an increased risk of incident CVD events, independent of traditional risk factors. Among the
best-studied negative emotions is anger. Population-based studies have demonstrated that the
experience of anger is a trigger of incident CVD events. The mechanism(s) by which provoked
anger acutely affects the pathways that underlie atherosclerosis development and progression
remain to be fully characterized.

Endothelial dysfunction is a promising mechanism that may explain the link between anger and
incident CVD events. Vascular endothelial cells (ECs) play essential roles in maintaining
vascular tone and the integrity of blood vessels. Evidence suggests that endothelial
dysfunction is an early pathogenic process underlying atherosclerosis development and CVD
event onset. Our preliminary findings show in apparently healthy individuals, an anger recall
task acutely induces endothelial dysfunction by impairing endothelium-dependent vasodilation,
injuring ECs, and disrupting the molecular processes underlying EC reparative capacity. We
have additionally found that this task may induce endogenous nitric oxide (NO) inhibition,
which plays a central role in aggravating endothelial dysfunction. Therefore, NO inhibition
may partially mediate anger-provoked endothelial dysfunction.

Although the strongest data are on anger-provoked CVD events, there is also some evidence
that the experience of other core negative emotions such as depressed mood and anxiety may
trigger CVD events. Whether the provocation of depressed mood and anxiety acutely induces
endothelial dysfunction and NO inhibition remains to be determined. The overall aim of this
study is to primarily examine the acute effects of provoked anger and secondarily depressed
mood and anxiety on EC health. We will also explore whether NO inhibition partially mediates
the acute effects of anger, depressed mood, and anxiety on endothelial function. Examination
of these critical pathways will help identify the biological pathways by which the experience
of core negative emotions leads to incident CVD risk.

To address these highly significant research questions, we propose a state-of-the-art,
laboratory-based, randomized controlled experiment in which 280 participants will be
randomized to one of four experimental conditions: an anger recall task (N=70), a depressed
mood recall task (N=70), an anxiety recall task (N=70), and an emotionally neutral condition
(N=70).

Inclusion Criteria:

- Age 18 and over

- Fluent in English

Exclusion Criteria:

- History of any chronic medical condition including prevalent CVD and traditional risk
factors

- Active smoking

- Chronic medication use, including over-the-counter drugs or herbal medications

- History of psychosis, a mood disorder, or any overt personality disorder

- Latex allergy

- Poor peripheral veins with low possibility of getting IV access