Low-density lipoprotein receptor-related protein in atherosclerosis development: up-regulation of gene expression in patients with coronary obstruction.
The low-density lipoprotein receptor-related protein (LRP) is a multifunctional cell-surface receptor that binds and mediates the endocytosis of several structurally and functionally distinct ligands. Involved in a variety of biological processes, including the regulation of the coagulation-fibrinolysis balance, the lipoprotein metabolism, cellular migration, proliferative processes and degenerative diseases, it has very recently become an interesting candidate for functional studies of the development of atherosclerosis. We investigated the individual cellular LRP gene expressions in 100 patients with angiographically confirmed severe coronary obstructions (myocardial infarction, patients with coronary angioplasty and patients with coronary bypass). Using a competitive reverse transcriptase polymerase chain reaction analysis we measured the specific LRP mRNA levels in monocytes from venous blood. In comparison with 110 unselected controls (122.1 ag/cell) the patient group demonstrated significantly higher LRP message levels (171.92 ag/cell). We found the most evident increase in the coronary angioplasty group (+43.5%). Investigating the intraindividual range of expression in healthy controls over a period of 4 weeks, we found nearly constant individual levels. Our results demonstrate a significant correlation of increased LRP mRNA levels with atherosclerotic processes (P<0.001), suggest an important implication of the LRP in atherosclerotic vascular processes, and emphasize the inclusion of LRP investigations in risk constellation studies.
Institute of Human Genetics and Medical Biology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.
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Handschug
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Schulz
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Schnürer
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Köhler
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Wenzel
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Teichmann
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Gläser
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics*; D003327:Coronary Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D012333:RNA, Messenger; D011971:Receptors, Immunologic