Electronic Theses and Dissertations

Date

2024

Document Type

Thesis

Degree Name

Master of Science

Department

Nutrition

Committee Chair

Lawrence Weiss

Committee Member

Brandt Pence

Committee Member

Yufeng Zhang

Committee Member

Marie van der Merwe

Committee Member

Liza Makowski

Abstract

Cardiovascular diseases, particularly atherosclerosis, pose significant health risks due to their association with endothelial dysfunction and chronic inflammation. Oxidized low-density lipoprotein (OxLDL) plays a pivotal role in atherosclerosis by inducing foam cell formation and promoting inflammatory responses in monocytes. This study investigates the impact of OxLDL on monocyte functions, specifically focusing on metabolic changes, inflammatory responses, and cellular senescence. Additionally, we explore the potential of Mdivi-1, a mitochondrial division inhibitor, in mitigating the detrimental effects of OxLDL. Human monocytes were treated with OxLDL, resulting in increased glycolytic activity, elevated expression of pro-inflammatory cytokines (IL-1β and CXCL8), and significant foam cell formation. These effects underscore the role of OxLDL in monocyte dysfunction and atherosclerosis progression. Mdivi-1 treatment effectively reversed the OxLDL-induced metabolic reprogramming, reduced the expression of inflammatory cytokines and inhibited foam cell formation, highlighting its therapeutic potential in atherosclerosis. Additionally, our findings challenge the traditional view that P16 and SA-β-Gal are reliable senescence markers, as P16 expression did not correlate with SA-β-Gal activity under high oxidative stress. Our study also revealed that P53 can be induced independently of P16, suggesting distinct regulatory mechanisms. This discrepancy highlights the complexity of cellular senescence and the need for comprehensive strategies in targeting it. These findings underscore the potential of Mdivi-1 in treating atherosclerosis and the importance of re-evaluating senolytic therapies.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

Notes

Open Access

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