title: Macrophage secretory activity and atherosclerosis during chronic renal failure.
abstract: Accelerated atherosclerosis is a serious complication of chronic renal failure (CRF) treated by peritoneal dialysis. In order to study the pathological mechanisms underlying its development we are using an animal model, namely the C57BL/6J mouse, which develops foam cell-type atherosclerotic lesions after surgical induction of CRF. During atherogenesis, monocyte/macrophages move from the circulation to the blood vessel wall, migrate through the endothelium, imbibe lipid and transform into foam cells. Migration through the endothelium involves proteolysis by plasminogen activator (PA) and uptake of lipids involves hydrolysis of lipoproteins by lipoprotein lipase (LPL). Both of these enzymes are secreted by macrophages. In this paper we report the results of studies on the effect of uremia on the secretion of PA and LPL by macrophages from C57BL/6J mice. The secretion of PA and LPL by macrophages from uremic mice (as defined by BUN levels) was higher than that by cells from control animals. Furthermore, whereas macrophage secretion of PA and LPL was significantly less in normal mice fed a high fat diet than in mice fed rodent chow, it was increased above control levels in uremic animals fed the atherogenic diet. We conclude that increased secretion of PA and LPL by macrophages may contribute to atherogenesis in uremic C57BL/6J mice.
authors.affiliation: Montreal General Hospital Research Institute.
authors.forename: J L
authors.initials: JL
authors.lastname: Stewart-Phillips
authors.forename: R F
authors.initials: RF
authors.lastname: Gagnon
authors.forename: B
authors.initials: B
authors.lastname: Stranix
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology*; D004036:Diet, Atherogenic; D005260:Female; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications*; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010960:Plasminogen Activators / Q000378:metabolism*
chemical_list: D008055:Lipids; D008071:Lipoprotein Lipase; D010960:Plasminogen Activators