Lysophosphatidic Acid Induction of Tissue Factor Expression in Aortic Smooth Muscle Cells
| Autor: | Marc S. Penn, Guy M. Chisolm, Essam M. Laag, Xuemin Xu, Allison L. Winokur, Jason R. Bydash, Mei-Zhen Cui, Guojun Zhao |
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| Rok vydání: | 2003 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Vascular smooth muscle RNA Stability p38 Mitogen-Activated Protein Kinases Muscle Smooth Vascular Thromboplastin chemistry.chemical_compound Tissue factor Internal medicine Lysophosphatidic acid medicine Animals Humans RNA Messenger Platelet activation Enzyme Inhibitors Phosphorylation Protein kinase A Aorta Cells Cultured Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinase 3 biology Kinase Heterotrimeric GTP-Binding Proteins Rats Cell biology Enzyme Activation Endocrinology Gene Expression Regulation Pertussis Toxin chemistry Mitogen-activated protein kinase biology.protein lipids (amino acids peptides and proteins) Lysophospholipids Mitogen-Activated Protein Kinases biological phenomena cell phenomena and immunity Cardiology and Cardiovascular Medicine |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 23:224-230 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Objective— Tissue factor (TF), the initiator of the coagulation cascade, is expressed by cells in atherosclerotic lesions. Lysophosphatidic acid (LPA) is a component of oxidized lipoproteins and an agent released by activated platelets. The present study investigated whether and how TF expression is regulated by LPA. Methods and Results— Northern blotting, Western blotting, and TF activity assays demonstrated that LPA markedly induced TF mRNA, protein, and activity in vascular smooth muscle cells. LPA-induced TF expression is primarily controlled at the transcriptional level. Phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signaling–regulated kinases (ERK1/2) was rapidly and markedly induced by LPA. MEK inhibitors U0126 and PD98059 blocked both ERK activation and the increase in TF mRNA. In contrast, the specific p38 MAP kinase inhibitor SB203580 had no effect on LPA-induced TF mRNA increase. The Gαi protein inhibitor, pertussis toxin, abolished LPA-induced phosphorylation of MEKs and ERKs, as well as the induction of TF mRNA. Conclusions— Our data demonstrate that a Gαi protein and activation of MEKs and ERKs mediate LPA-induced TF expression. Our data suggest that elevated LPA could be a thrombogenic risk factor by upregulating TF expression. These results may have important implications in vascular remodeling and vascular diseases. |
| Databáze: | OpenAIRE |
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