Date of Award


Degree Name

Doctor of Philosophy



First Advisor

Dr. Bradley E. Huitema

Second Advisor

Dr. John Mason

Third Advisor

Dr. Sue Stapleton


Coronary heart disease continues to be the leading cause of death in the affluent world. Despite identification of several risk factors for coronary heart disease (age, sex, lipoprotein profile, hypertension, diabetes, cigarette smoking, obesity), a significant amount of variability associated with the incidence of coronary heart disease cannot be explained solely on the basis of these risk factors. The contribution of psychosocial factors to the development of coronary heart disease (type A behavior, social isolation, traumatic events, unstable social conditions) continues to be a promising area of investigation. However, a biochemical pathway linking psychosocial factors to coronary heart disease remains unclear.

The present study investigates the extent to which hormones (epinephrine, norepinephrine and cortisol) released during emotional arousal contribute to atherogenesis by enhancing the activity of an enzyme, acylCoA: cholesterol acyltransferase (ACAT), which esterifies cholesterol in the arteiy wall. Rat hepatoma cells (Fu5AH) were incubated with [1-^14C]oleate in the presence of epinephrine, norepinephrine and cortisol in three serum conditions (hyperlipemic, normolipemic and serum-free medium). Lipid was extracted from the cells and separated. The radioactivity of the lipid fractions is a measure of the incorporation of [1-^14C]oleate into phospholipids, triglycerides and cholesteryl ester. A slight increase in cholesteryl ester synthesis (ACAT activity) was observed across all serum conditions in cells incubated with epinephrine compared to controls. Cells incubated with cortisol showed a decrease in ACAT activity compared to controls.

Despite constancy of well known risk factors, the persistent variability of the incidence and severity of atherosclerosis needs to be explained. The present finding that ACAT activity is enhanced by epinephrine, provides a possible mechanism linking psychosocial factors and coronary heart disease.

Access Setting

Dissertation-Open Access