UBC Theses and Dissertations
The influence of different plasma lipoprotein fractions and macrophages on smooth muscle cell foam cell formation Ortega, Carleena Angelica S.
Atherosclerosis, which manifests clinically as ischemic cardiovascular disease (CVD), is the leading cause of global mortality. From a lipid standpoint, CVD risk has traditionally been assessed by measuring low-density lipoprotein (LDL) cholesterol in the fasted state. Recently, both the measurement of the complete non-high-density lipoprotein (non-HDL) cholesterol fraction and the lipids in the nonfasting state have gained traction as better indicators of CVD risk and prevention. In addition, while macrophages in atherosclerotic lesions have been the focus of most plaque cholesterol metabolism studies, growing evidence suggests that smooth muscle cells (SMCs) are the key cell type driving initial lesion development and the main cell type contributing to cholesterol-overloaded “foam cells” in these lesions. Further evidence suggests that macrophages and SMCs may influence each other’s tendency to become foam cells. The current study’s aims are to compare the effects of LDL and non-HDL from both fasting and nonfasting plasma on the lipid loading of SMCs and macrophages, and the effects of SMC-macrophage coculture on the tendency of each cell type to become foam cells in vitro. We hypothesized that the nonfasting lipoproteins, the non-HDL fractions, and coculture with macrophages will promote more SMC foam cells compared with the fasting lipoproteins, LDL fractions, and monoculture. Our results show that lipoprotein loading of human SMCs have a trend of higher cholesterol accumulation with fasting and non-HDL fractions via cholesterol mass quantification with mass spectrometry. However, flow cytometry analysis demonstrated a trend of more BODIPY-high SMCs with the nonfasting and non-HDL fractions whether in monoculture or direct co-culture with macrophages. Coculture demonstrated a trend of more BODIPY-high SMCs in the presence of the non-fasting non-HDL compared with the monocultured SMCs. Monocultured macrophage demonstrated a trend of higher cholesterol accumulation in the presence of fasting lipoproteins and non-HDL fraction compared with the non-fasting lipoproteins and the LDL fraction. These preliminary findings indicate that the atherogenicity of the non-fasting and non-HDL fractions in vivo may be apparent in in vitro cell culture studies via the increased foam cell formation of SMCs and macrophages when incubated with these fractions.
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