Dimethyl sulfoxide inhibits tissue factor expression, thrombus formation, and vascular smooth muscle cell activation: a potential treatment strategy for drug-eluting stents
| Autor: | Zhihong Yang, Giovanni G. Camici, Kushiar Shojaati, Nicola Schäfer, Urs Schulz, Jan Steffel, Felix C. Tanner, Christian M. Matter, Thomas F. Lüscher, Alexander Akhmedov, Jeannette Baldinger |
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| Rok vydání: | 2006 |
| Předmět: |
Vascular smooth muscle
Myocytes Smooth Muscle 030204 cardiovascular system & hematology Pharmacology Muscle Smooth Vascular Thromboplastin 03 medical and health sciences chemistry.chemical_compound Tissue factor Mice 0302 clinical medicine Thrombin Cell Movement Physiology (medical) medicine Myocyte Animals Humans Dimethyl Sulfoxide Carotid Artery Thrombosis Cells Cultured 030304 developmental biology Cell Proliferation 0303 health sciences business.industry Dimethyl sulfoxide Thrombosis 3. Good health Disease Models Animal chemistry Gene Expression Regulation Immunology Trypan blue Tumor necrosis factor alpha Cardiology and Cardiovascular Medicine business Cell activation medicine.drug |
| Zdroj: | Circulation. 114(14) |
| ISSN: | 1524-4539 |
| Popis: | Background— Subacute stent thrombosis is a major clinical concern, and the search for new molecules to cover stents remains important. Dimethyl sulfoxide (DMSO) is used for preservation of hematopoietic progenitor cells and is infused into patients undergoing bone marrow transplantation. Despite its intravenous application, the impact of DMSO on vascular cells has not been assessed. Methods and Results— In human endothelial cells, monocytes, and vascular smooth muscle cells (VSMC), DMSO inhibited tissue factor (TF) expression and activity in response to tumor necrosis factor-α or thrombin in a concentration-dependent manner. DMSO did not exert any toxic effects as assessed by phase-contrast microscopy, trypan blue exclusion, and lactate dehydrogenase release. Real-time polymerase chain reaction revealed that inhibition of TF expression occurred at the mRNA level. This effect was mediated by reduced activation of the mitogen-activated protein kinases c-Jun terminal NH 2 kinase (51±6%; P =0.0005) and p38 (50±3%; P P =NS). In contrast to TF, DMSO did not affect expression of TF pathway inhibitor or plasminogen activator inhibitor-1. In vivo, DMSO treatment suppressed TF activity (41%; P P =0.005) and migration (77%; P =0.0001) in a concentration-dependent manner; moreover, it prevented rapamycin and paclitaxel-induced upregulation of TF expression. Conclusions— DMSO suppresses TF expression and activity, as well as thrombus formation; in addition, it inhibits VSMC proliferation and migration. Given its routine use in modern clinical practice, we propose DMSO as a novel strategy for coating drug-eluting stents and treating acute coronary syndromes. |
| Databáze: | OpenAIRE |
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