Atherosclerosis is a chronic inflammatory and lipid disorder caused by the
buildup of cholesterol-loaded cells of monocyte and muscle cell origin in the arterial
intima. While the relationship between excess cholesterol and macrophage behavior
is well observed, the molecular mechanisms linking the two remain unclear.
Therefore, characterizing the pathways from changes in intracellular cholesterol to
the resulting inflammatory output is key to understanding the behavioral changes
observed in human macrophages in vitro. We identified that THP-1 macrophages
acutely depleted of cholesterol increase the expression of JMJD3, an H3K27me3
demethylase. By using IL-10 as a marker for immune-modulating genes and TNF-α
as a marker for pro-inflammatory genes, cholesterol-depleted THP-1 macrophages
responded inconsistently to LPS and echinomycin, an inhibitor of HIF-1α, as
determined by RT-qPCR and ELISA. Further studies investigating other regulators
and outputs of macrophage behavior linked to cellular cholesterol modification are
required.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/43459 |
| Date | 12 April 2022 |
| Creators | Aycan, Dila |
| Contributors | Zha, Xiaohui |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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