VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor
The potential role of the very low density lipoprotein (VLDL) receptor in mediating VLDL-induced plasminogen activator inhibitor-1 (PAI-1) expression was studied in vitro. Cultured endothelial cells incubated with VLDL showed an increased secretion of PAI-1. This response to VLDL could be completely...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
1999-05-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752032126X |
| _version_ | 1818739608866783232 |
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| author | Lennart Nilsson Mats Gåfvels Leena Musakka Katharina Ensler Dudley K. Strickland Bo Angelin Anders Hamsten Per Eriksson |
| author_facet | Lennart Nilsson Mats Gåfvels Leena Musakka Katharina Ensler Dudley K. Strickland Bo Angelin Anders Hamsten Per Eriksson |
| author_sort | Lennart Nilsson |
| collection | DOAJ |
| description | The potential role of the very low density lipoprotein (VLDL) receptor in mediating VLDL-induced plasminogen activator inhibitor-1 (PAI-1) expression was studied in vitro. Cultured endothelial cells incubated with VLDL showed an increased secretion of PAI-1. This response to VLDL could be completely prevented by the receptor-associated protein (RAP) and partially blocked by rabbit polyclonal anti-VLDL receptor IgG. Furthermore, Chinese hamster ovary (CHO) control cells and cells overexpressing the VLDL receptor were transiently transfected with a PAI-1 promoter–reporter construct and incubated with VLDL. The PAI-1 promoter activity in response to VLDL was significantly higher in the VLDL receptor overexpressing cells compared to the control cells. Addition of RAP completely blocked the VLDL-activated PAI-1 transcription. Electromobility shift assay was performed to investigate whether the enhanced PAI-1 promoter activity seen in the VLDL receptor overexpressing cells in response to VLDL involved induction of the previously described VLDL-inducible factor(s) binding to the –675 to –653 region of the PAI-1 promoter. We found that the binding of the VLDL-inducible factor in VLDL receptor overexpressing cells was markedly enhanced by addition of VLDL as compared to control cells where no increased binding could be seen in response to VLDL. In summary, these results indicate that the VLDL receptor is a strong candidate for mediating VLDL effects on PAI-1 synthesis and secretion in cells expressing this receptor.—Nilsson, L., M. Gåfvels, L. Musakka, K. Ensler, D. K. Strickland, B. Angelin, A. Hamsten, and P. Eriksson. VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor. J. Lipid Res. 1999. 40: 913–919. |
| first_indexed | 2024-12-18T01:27:33Z |
| format | Article |
| id | doaj.art-7f34a73bfa334f6f9e9759ac046c73d9 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-18T01:27:33Z |
| publishDate | 1999-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-7f34a73bfa334f6f9e9759ac046c73d92022-12-21T21:25:41ZengElsevierJournal of Lipid Research0022-22751999-05-01405913919VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptorLennart Nilsson0Mats Gåfvels1Leena Musakka2Katharina Ensler3Dudley K. Strickland4Bo Angelin5Anders Hamsten6Per Eriksson7To whom correspondence should be addressed.; Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, S-171 76 Stockholm, SwedenCenter for Metabolism and Endocrinology, Department of Medicine, and Molecular Nutrition Unit, Center for Nutrition and Toxicology, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, SwedenAtherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, S-171 76 Stockholm, SwedenCenter for Metabolism and Endocrinology, Department of Medicine, and Molecular Nutrition Unit, Center for Nutrition and Toxicology, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, SwedenDepartment of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, MD 20855Center for Metabolism and Endocrinology, Department of Medicine, and Molecular Nutrition Unit, Center for Nutrition and Toxicology, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, SwedenAtherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, S-171 76 Stockholm, SwedenAtherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, S-171 76 Stockholm, SwedenThe potential role of the very low density lipoprotein (VLDL) receptor in mediating VLDL-induced plasminogen activator inhibitor-1 (PAI-1) expression was studied in vitro. Cultured endothelial cells incubated with VLDL showed an increased secretion of PAI-1. This response to VLDL could be completely prevented by the receptor-associated protein (RAP) and partially blocked by rabbit polyclonal anti-VLDL receptor IgG. Furthermore, Chinese hamster ovary (CHO) control cells and cells overexpressing the VLDL receptor were transiently transfected with a PAI-1 promoter–reporter construct and incubated with VLDL. The PAI-1 promoter activity in response to VLDL was significantly higher in the VLDL receptor overexpressing cells compared to the control cells. Addition of RAP completely blocked the VLDL-activated PAI-1 transcription. Electromobility shift assay was performed to investigate whether the enhanced PAI-1 promoter activity seen in the VLDL receptor overexpressing cells in response to VLDL involved induction of the previously described VLDL-inducible factor(s) binding to the –675 to –653 region of the PAI-1 promoter. We found that the binding of the VLDL-inducible factor in VLDL receptor overexpressing cells was markedly enhanced by addition of VLDL as compared to control cells where no increased binding could be seen in response to VLDL. In summary, these results indicate that the VLDL receptor is a strong candidate for mediating VLDL effects on PAI-1 synthesis and secretion in cells expressing this receptor.—Nilsson, L., M. Gåfvels, L. Musakka, K. Ensler, D. K. Strickland, B. Angelin, A. Hamsten, and P. Eriksson. VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor. J. Lipid Res. 1999. 40: 913–919.http://www.sciencedirect.com/science/article/pii/S002222752032126XatherosclerosistransfectionVLDL response element |
| spellingShingle | Lennart Nilsson Mats Gåfvels Leena Musakka Katharina Ensler Dudley K. Strickland Bo Angelin Anders Hamsten Per Eriksson VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor Journal of Lipid Research atherosclerosis transfection VLDL response element |
| title | VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor |
| title_full | VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor |
| title_fullStr | VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor |
| title_full_unstemmed | VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor |
| title_short | VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor |
| title_sort | vldl activation of plasminogen activator inhibitor 1 pai 1 expression involvement of the vldl receptor |
| topic | atherosclerosis transfection VLDL response element |
| url | http://www.sciencedirect.com/science/article/pii/S002222752032126X |
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