BMP-2 gene expression and effects on human vascular smooth muscle cells
| Autor: | Juan L. Gu, Paul G. Lysko, Tian-Li Yue, Karen M. Anderson, Robert N. Willette, Heather Minehart |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Umbilical Veins
Platelet-derived growth factor Vascular smooth muscle Physiology medicine.medical_treatment Bone Morphogenetic Protein 2 Gene Expression Bone morphogenetic protein Muscle Smooth Vascular chemistry.chemical_compound Cell Movement Transforming Growth Factor beta medicine Humans Aorta Cells Cultured Platelet-Derived Growth Factor biology Reverse Transcriptase Polymerase Chain Reaction Growth factor Chemotaxis Cell migration Drug Synergism Recombinant Proteins Cell biology medicine.anatomical_structure chemistry embryonic structures Immunology Bone Morphogenetic Proteins biology.protein Cardiology and Cardiovascular Medicine Platelet-derived growth factor receptor Cell Division Blood vessel |
| Zdroj: | Journal of vascular research. 36(2) |
| ISSN: | 1018-1172 |
| Popis: | Bone morphogenetic proteins (BMPs) and their serine/threonine kinase receptors have been identified in atherosclerotic arteries and vascular smooth muscle cells, respectively. Thus, BMPs (the largest subfamily of the TGF-β superfamily) have been implicated in the pathogenesis of atherosclerosis. However, the origins of BMP biosynthesis and the functional roles of BMP in blood vessels are unclear. The present study explored BMP-2 gene expression in various human blood vessels and vascular cell types. Functional in vitro studies were also performed to determine the effects of recombinant human BMP-2 on migration (transwell assay) and proliferation ([3H]-thymidine incorporation) of human aortic vascular smooth muscle cells (HASMC). RT-PCR experiments revealed BMP-2 gene expression in normal and atherosclerotic human arteries as well as cultured human aortic and coronary vascular smooth muscle cells, human umbilical vein endothelial cells (HUVECs) and human macrophages. In cellular migration studies, incubation with BMP-2 produced efficacious (≤610-fold), concentration- and time-dependent chemotaxis of HASMCs (EC50 = 0.8 μM) with little or no effect on HUVEC chemotaxis. The increased HASMC motility induced by BMP-2 was inhibited by coincubation with an anti-BMP-2 mAb. In addition, subthreshold concentrations of BMP-2 produced a dramatic synergistic effect upon platelet-derived growth factor (PDGF)-induced chemotaxis. In contrast to PDGF, BMP-2 had no significant effet on [3H]-thymidine incorporation in HASMC at chemotaxic concentrations (≤6.0 μM) nor did it synergize with the mitogenic effects of PDGF. In conclusion, the expression of BMP-2 by numerous cell types in the blood vessel wall may play a chemotactic or cochemotactic role in the smooth muscle cell response to vascular injury. |
| Databáze: | OpenAIRE |
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