Title

The influence of oxytocin on oxidative and inflammatory mechanisms in the progression of atherosclerosis in human vascular cells

Date of Award

2006

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Psychology

First Committee Member

Philip M. McCabe, Committee Chair

Second Committee Member

Armando J. Mendez, Committee Member

Abstract

Previously, we examined the effects of chronic behavioral stressors and social environment on the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit (WHHL) (McCabe et al., 2002). A major finding was that a stable social environment attenuated the progression of disease compared to an unstable or individually-caged social environment illustrating the importance of behavioral factors in atherogenesis using an experimental animal model with strong genetic determinants. It has been suggested that the neuropeptide oxytocin plays an important role in affiliative social behavior and may be involved in slowing the progression of atherosclerosis through antioxidant and anti-inflammatory mechanisms.The current study used in-vitro methods to examine the influence of oxytocin on oxidative and inflammatory mechanisms in cultured human vascular endothelial and smooth muscle cells, as well as monocytes and macrophages. Primary dependent measures included oxytocin receptor protein and mRNA expression, NADPH oxidase activity, and cell adhesion molecule expression using immunoblotting and flow cytometry. Results demonstrated for the first time the presence of oxytocin receptors in monocytes and macrophages. Oxytocin receptor protein and mRNA expression were also confirmed in aortic endothelial and aortic smooth muscle cells. NADPH oxidase activity was decreased in aortic endothelial cells, aortic smooth muscle cells, THP-1 monocytes, and THP-1 macrophages treated with oxytocin. In addition, aortic endothelial cells stimulated with TNF-alpha and co-incubated with oxytocin decreased the protein expression of the adhesion molecules ICAM and VCAM compared to cells treated only with TNF-alpha. This result was also confirmed by looking at the surface expression of ICAM in aortic endothelial cells using flow cytometry. These are novel findings suggesting oxytocin may contribute to an additive effect of decreased superoxide production and inflammation that may slow the progression of atherosclerosis.

Keywords

Psychology, Behavioral; Health Sciences, Pharmacology; Psychology, Physiological

Link to Full Text

http://access.library.miami.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3240849