Innate immune protein C1q plays a dual role in atherosclerosis. In early stages, C1q plays a protective role, but the mechanism is not fully understood. Autophagy is a catabolic pathway that has shown to play a role in cellular survival and is an important process in many phagocytic cells, such as macrophages. We hypothesize that complement C1q increases autophagy in macrophages during clearance of modified lipoprotein and acts in an atheroprotective manner to increase macrophage survival. We examined the influence of C1q on macrophage autophagy markers Atg5, Beclin 1, LC3B-II, and p62 during clearance of oxidized LDL. Levels of initiation and elongation protein, Beclin 1 and Atg5, are not modulated by C1q, but levels of autophagosome proteins, LC3B-II and p62, were increased in immunoblot. Quantitative PCR revealed that the increase in p62 protein levels was not due to an increase in transcription. Immunofluorescence microscopy verified that the increase in LC3B and p62 by C1q resulted in an increase in autophagosome formation during oxLDL and acLDL clearance. TEM verified the formation of double membrane vesicles. By inhibiting autolysosome maturation with chloroquine during modified LDL clearance, C1q modulation of autophagy was found to not have an effect on macrophage survival. These findings further our knowledge of C1q protective mechanisms, and the goal of developing future atherosclerosis therapies.
|Advisor:||Fraser, Deborah A.|
|Commitee:||Eldon, Elizabeth, Gharakhanian, Editte|
|School:||California State University, Long Beach|
|School Location:||United States -- California|
|Source:||MAI 56/02M(E), Masters Abstracts International|
|Keywords:||Atherogenic lipoproteins, Atherosclerosis, Autophagy, Complement, Lipoprotein, Macrophage|
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