Publication Date

2014-10-29

Availability

Embargoed

Embargo Period

2016-10-28

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Psychology (Arts and Sciences)

Date of Defense

2014-09-23

First Committee Member

Philip M. McCabe

Second Committee Member

Armando J. Mendez

Third Committee Member

Neil Schneiderman

Fourth Committee Member

Maria M. Llabre

Fifth Committee Member

Julia Zaias

Sixth Committee Member

Michael H. Antoni

Abstract

Behavioral and psychosocial factors have been shown to influence cardiovascular disease. While interventions targeting these risk factors demonstrate clinical improvement, mechanisms underlying these effects remain to be determined. Research has also defined a relationship between psychosocial stress and immune function, and revealed stress related increases in lymphatic sympathetic nerve density. Considering that inflammation characterizes the various stages of heart disease, the current study assessed whether social stress could influence vascular sympathetic innervation in the presence or absence of hypercholesterolemia. We found dense sympathetic innervation extending into the vascular media and intima throughout the aortic arch and thorax in diseased as well as non-diseased animals. To our knowledge, this is the first demonstration of extensive sympathetic innervation in all layers of normal vessels. Compared to NZW animals, WHHL rabbits displayed increased sympathetic innervation and a relationship between sympathetic varicosity counts and lesion severity, suggesting that innervation increases with hypercholesterolemia and advanced disease. In hypercholesterolemic animals, rabbits within a socially unstable environment showed more agonistic behavior and atherosclerosis than rabbits in a socially stable condition. Contrary to our hypothesis, however, we did not find evidence for an effect of social environment on sympathetic innervation. Reasons for this null outcome are proposed and alternative mechanistic links between social behavior and heart disease are discussed. This novel study provided insight on the brain-immune connection within the vasculature, identifying factors influencing innervation density, and potentially mediating disease.

Keywords

Cardiovascular Disease; Atherosclerosis; Hyperlipidemia; Sympathetic Innervation; Rabbit

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