Atherosclerosis is a chronic inflammatory disease characterized by the development of plaque in arteries. Interactions between monocytes/macrophages, endothelial cells and lipoproteins play a major role in the disease pathogenesis. C1q is an innate immune protein traditionally known for activation of the complement cascade, leading to inflammation which exacerbates atherosclerosis. However, we previously showed that C1q bound to modified lipoproteins (e.g. oxidized LDL) plays a protective role by polarizing macrophages towards an anti-inflammatory state during engulfment and increasing survival and efferocytotic function of macrophage foam cells. Additionally, C1q modulates macrophage chemokine production in in vitro and in in vivo models of atherosclerosis. Here we investigate C1q modulation of both endothelial cell chemokine production, and functions affecting monocyte migration. Human aortic endothelial cells (HAEC) were incubated with oxLDL +/- C1q. RNA and supernatants were collected for chemokine gene regulation and protein analysis, respectively. Monocyte adhesion, endothelial permeability and wound healing properties as well as transendothelial migration were also measured. The data show that C1q modulates chemokine production and HAEC monolayer permeability and increases monocyte adhesion, wound healing and transendothelial migration. Thus, C1q interactions with HAEC in hyperlipidemic conditions may result in increased availability of phagocytes for clearance in the early atherosclerotic lesion. However, in later stages infiltrating cells may contribute to disease progression through an increased proinflammatory environment and complement activation. Understanding timing and molecular mechanisms in atherosclerosis will be vital for the development of novel treatments.
|Commitee:||Gharakhanian, Editte, Narayanaswami, Vasanthy|
|School:||California State University, Long Beach|
|School Location:||United States -- California|
|Source:||MAI 82/6(E), Masters Abstracts International|
|Subjects:||Microbiology, Cellular biology, Genetics, Molecular biology, Pathology|
|Keywords:||Atherosclerosis, C1q, Endothelial cells, Monocyte, oxLDL, Inflammatory disease, Plaque, Artery clogging, In vivo, In vitro, Gene regulation, Disease progression, Molecular mechanisms|
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