Atherosclerotic cardiovascular disease (CVD) is hallmarked by inflammatory immune activation, particularly by the induction of a response by monocytes. Classical (CD14++CD16-) are anti-inflammatory mediators under homeostatic conditions, while intermediate (CD14++CD16+) and non-classical (CD14LowCD16++) monocytes promote inflammation following activation. Monocyte activation and functionality is dependent upon receptor expression and ligand production by a variety of cells, including monocytes. Alterations in the expression of surface receptors often have a direct impact upon monocyte function, such as the increased pro-inflammatory cytokine production in response to activation that accompanies elevated CD14 expression or increased chemotaxis that is elicited by increased CCR2 expression. Ligand-receptor interactions also play a significant role in cell fate, including survival, proliferation, and differentiation. Monocytes are capable of differentiating into phagocytic cells known as macrophages in response to specific ligand-receptor interactions. Macrophages play a significant role in the pathogenesis and progression of CVD. Imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages can to lead disease development and progression, such as the skewing toward the M1 phenotype that occurs in CVD. Elucidation of these mechanisms will allow for the development of targeted interventions, including pharmacological and non-pharmacological physical interventions, such as physical exercise. Therefore, this dissertation investigates the role of CD14 and CCR2 monocyte subset receptors that impact immune-mediated inflammation following ST segment elevation myocardial infarction (STEMI) as well as physical activity and cardiorespiratory endurance related differences in the acute exercise response of monocyte signaling, recruitment, and macrophage polarization and their potential role in CVD prevention.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-6723 |
| Date | 01 January 2018 |
| Creators | Blanks, Anson M |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © Anson Blanks |
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