Expression of LDL receptor-related protein/alpha 2-macroglobulin receptor in human normal and atherosclerotic arteries.
Low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2-MR) is a multifunctional cell-surface receptor that is responsible for the clearance of lipoprotein remnants, proteases, or cytokines/growth factors in complex with alpha 2-macroglobulin as well as of plasminogen activators complexed with inhibitors. We investigated the expression of LRP/alpha 2-MR in healthy and atherosclerotic human arteries by in situ hybridization using an LRP/alpha 2-MR mRNA-specific riboprobe and immunocytochemistry using specific monoclonal antibodies. The cell types expressing LRP/alpha 2-MR were identified by immunolabeling of antigens specific for endothelial cells, smooth muscle cells, and macrophages. In normal arteries, LRP/alpha 2-MR mRNA and protein were found in smooth muscle cells of the media and vasa vasorum and in adventitial fibroblasts. Endothelial cells were negative for LRP/alpha 2-MR protein but positive for its mRNA. Atherosclerotic arteries exhibited a strong labeling for LRP/alpha 2-MR mRNA and protein that was observed in intimal smooth muscle cells exhibiting normal or foam cell characteristics and in lipid-laden cells positive for macrophage markers. A particularly high expression was detected in macrophages located in the cap of the lipid-rich necrotic core. These results suggest that cellular components of the atherosclerotic plaque express LRP/alpha 2-MR. This receptor may play an important local scavenger role for lipoprotein remnants, for growth factors/cytokines, and for extracellular protease-inhibitor complexes.
Lupu
F
F
Hematology Division, University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Heim
D
D
Bachmann
F
F
Kruithof
E K
EK
D001158:Arteries / Q000737:chemistry / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis*; D011971:Receptors, Immunologic / Q000235:genetics*
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D015347:RNA Probes; D012333:RNA, Messenger; D011971:Receptors, Immunologic