J. Biochem, 1998, Vol. 123, No. 6 1119-1126
© 1998 Japanese Biochemical Society
research-article |
Changes of Gene Expression by Lysophosphatidylcholine in Vascular Endothelial Cells: 12 Up-Regulated Distinct Genes Including 5 Cell Growth-Related, 3 Thrombosis-Related, and 4 Others1
National Cardiovascular Center Research Institute 5-7-1 Fujishirodai, Suita, Osaka 565-8565
3 To whom correspondence should be addressed. Tel: +81-6-833-5012 (Ext. 2460), Fax: +81-6-872-8091, E-mail: miyata{at}ri.ncvc.go.jp
Lysophosphatidylcholine (lysoPC), a component of oxidatively modified lipoproteins, is present in atherosclerotic lesions, and its proatherogenic properties have been demonstrated. To gain an insight into lysoPC-mediated endothelial gene expression, we applied nonradioactive differential display analysis of mRNA from lysoPC-treated and untreated human umbilical vein endothelial cells. We identified 12 up-regulated distinct genes including 5 cell growth-related genes (two phosphatases CL100 and B23/hVH-3, gravin, activating transcription factor-4, and heparin-binding epidermal growth factor-like growth factor), 3 thrombosis-related genes (plasminogen activator inhibitor-1, tissue plasminogen activator, and thrombomodulin), and 4 others (stanniocalcin, NAD-dependent methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase, BENE, and reducing agents and tunicamycin-responsive protein). We isolated a full-length cDNA of human gravin. The cDNA sequence of gravin was homologous with rat mitogenic regulatory gene or rat protein kinase C binding protein and substrate, suggesting that gravin would regulate cell growth. Thus, lysoPC apparently accelerates atherosclerosis by regulating the expression of a wide variety of genes. Our data suggest the involvement in atherogenesis of the genes hitherto regarded as atherosclerosis-unrelated.
1 This work was supported in part by Grants-in-Aid from Special Coordination Funds for Promoting Science and Technology (Encouragement System of COE), the Science and Technology Agency of Japan and from the Ministry of Education, Science, Sports and Culture of Japan. The nucleotide sequence data of human gravin appears in the DDBJ, EMBL, and GenBank nucleotide sequence databases with the accession number AB003476.
2 Present address: The First Department of Internal Medicine, Niigata University School of Medicine, Niigata 951-8510.
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