C1q plays a dual role in atherosclerosis, activating the inflammatory complement cascade but in later stages, restricts early progression of the disease. We hypothesize that independent of its role in the complement innate immune system, C1q will modulate macrophages towards a resolving phenotype leading to a reduction in inflammation and disease pathology. Low-density lipoprotein receptor and C1q deficient hyperlipidemic mice were used to examine the effects of C1q on disease pathology. Mice were fed a regular or high fat diet to mimic early verses late stage disease. C1q reduced lesion size and cholesterol levels in early stages of disease. Plasma levels of disease markers sP-selectin, sICAM-1, PAI-1 and thrombomodulin were modulated by C1q. RNA-sequencing was used to elucidate biological pathways modulated by C1q during atherogenesis in aortic-lesional macrophages. Genes involved in cellular catabolism, cytoskeletal rearrangement and endocytosis were differentially modulated by C1q. These findings further our knowledge of the protective role in early atherosclerosis by C1q and may provide insight into novel therapeutic pathways.
|Advisor:||Fraser, Deborah A.|
|Commitee:||Brusslan, Judy, Sinchak, Kevin|
|School:||California State University, Long Beach|
|School Location:||United States -- California|
|Source:||MAI 57/06M(E), Masters Abstracts International|
|Subjects:||Molecular biology, Cellular biology, Immunology|
|Keywords:||Atherosclerosis, Cellular catabolism, Cytoskeletal rearrangement, Endocytosis, Innate, Macrophage|
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