Defense Date

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Rehabilitation and Movement Science

First Advisor

Dr. Edmund O. Acevedo

Second Advisor

Dr. Jennifer K. Stewart

Third Advisor

Dr. John J. Ryan

Fourth Advisor

Dr. Robert Lee Franco

Fifth Advisor

Dr. Ryan S. Garten

Abstract

Pentraxin 3 (PTX3) is a vital regulator of innate immune function that has been shown to counterregulate pro-inflammatory signaling and protect against the development of cardiovascular disease (CVD). Less is known about how PTX3 may mitigate against CVD risk by regulating the pro-inflammatory response at the cellular level. Therefore, this dissertation details four manuscripts which aimed to examine the capacity of PTX3 to regulate the innate immune response of peripheral blood mononuclear cells (PBMCs) isolated from healthy adults. Manuscript 1 examined the capacity of PTX3 to alter the inflammatory milieu following in vitro stimulation of isolated PBMCs with the pro-inflammatory lipid palmitate. In addition, Manuscript 2 sought to examine how participation in acute exercise, a powerful anti-inflammatory behavior that reduces CVD risk, alters the inflammatory phenotype and response of mononuclear cells following ex vivo stimulation with lipopolysaccharide (LPS). Manuscript 3 aimed to further elucidate the potential impact of cardiorespiratory fitness on the capacity of PTX3 to stimulate an innate immune response prior to and immediately following acute exercise in aerobically trained and untrained individuals. Finally, Manuscript 4 investigated the impact of healthy aging on plasma PTX3 concentrations and its relationship with telomere length in middle-aged compared to young adults. The capacity of isolated PBMCs to express a key cellular mechanism involved in maintaining longer telomere lengths, human telomerase reverse transcriptase (hTERT), following cellular stimulation with LPS, PTX3, and PTX3+LPS was also examined to address a mechanism that might explain how persistent exposure of circulating immune cells to the age-related pro-inflammatory milieu contributes to the shortening of telomere lengths.

Rights

© Aaron L. Slusher

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

4-16-2018

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