Sphingosine-1-phosphate receptor 3 promotes neointimal hyperplasia in mouse iliac-femoral arteries
| Autor: | Frank Dastvan, Michael A. Reidy, Takuya Shimizu, Axel Larena-Avellaneda, Allison De Wispelaere, Aesim Cho, Guenter Daum, Lihua Chen, Martin Sebastian Winkler, Jacob Caylor, Jessie Deou, Travis D'Souza |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Pathology medicine.medical_specialty Intimal hyperplasia Time Factors Biology Transfection Iliac Artery Article Mice Restenosis Cell Movement Sphingosine medicine Animals Humans Extracellular Signal-Regulated MAP Kinases Sphingosine-1-Phosphate Receptors Cells Cultured Cell Proliferation Neointimal hyperplasia S1PR3 Mice Knockout Hyperplasia Vascular disease Vascular System Injuries medicine.disease rac GTP-Binding Proteins Rac GTP-Binding Proteins Femoral Artery Mice Inbred C57BL Disease Models Animal Receptors Lysosphingolipid medicine.anatomical_structure Carotid Arteries Immunology Lysophospholipids Cardiology and Cardiovascular Medicine Tunica Intima Proto-Oncogene Proteins c-akt Artery Signal Transduction |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 32(4) |
| ISSN: | 1524-4636 |
| Popis: | Objective— The objective of this study was to define a role for sphingosine-1-phosphate receptor 3 (S1PR3) in intimal hyperplasia. Methods and Results— A denudation model of the iliac-femoral artery in wild-type and S1PR3-null mice was used to define a role for S1PR3 in the arterial injury response because we found in humans and mice that expression of S1PR3 was higher in these arteries compared with carotid arteries. At 28 days after surgery, wild-type arteries formed significantly larger lesions than S1PR3-null arteries. Bromodeoxyuridine labeling experiments demonstrated that on injury, wild-type arteries exhibited higher medial as well as intimal proliferation than S1PR3-null arteries. Because S1PR3 expression in vitro was low, we expressed S1PR3 in S1PR3-null smooth muscle cells (SMCs) using retroviral-mediated gene transfer to study the effects of S1PR3 on cell functions and signaling. SMCs expressing S1PR3, but not vector-transfected controls, responded to sphingosine-1-phosphate stimulation with activation of Rac, Erk, and Akt. SMCs expressing S1PR3 also migrated more. Conclusion— In humans and mice, S1PR3 expression was higher in iliac-femoral arteries compared with carotid arteries. S1PR3 promoted neointimal hyperplasia on denudation of iliac-femoral arteries in mice, likely by stimulating cell migration and proliferation through activation of signaling pathways involving Erk, Akt, and Rac. |
| Databáze: | OpenAIRE |
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