Dimethyl sulfoxide inhibits tissue factor expression, thrombus formation, and vascular smooth muscle cell activation: a potential treatment strategy for drug-eluting stents
- Camici, Giovanni G. Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland
- Steffel, Jan Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland
- Akhmedov, Alexander Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland
- Schafer, Nicola Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland
- Baldinger, Jeannette Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland
- Schulz, Urs Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland
- Shojaati, Kushiar Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland
- Matter, Christian M. Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland - Cardiovascular Center, University Hospital Zürich, Switzerland
- Yang, Zhihong Physiology Institute, Faculty of Medicine, University of Fribourg, Switzerland
- Lüscher, Thomas F. Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland - Cardiovascular Center, University Hospital Zürich, Switzerland
- Tanner, Felix C. Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland - Cardiovascular Center, University Hospital Zürich, Switzerland
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25.09.2006
Published in:
- Circulation. - 2006, vol. 114, no. 14, p. 1512-1521
English
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-***Missing image substitution*** 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 NH₂ kinase (51±6%; P=0.0005) and p38 (50±3%; P<0.0001) but not p44/42 (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<0.002) and prevented thrombotic occlusion in a mouse carotid artery photochemical injury model. DMSO also inhibited VSMC proliferation (70%; 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.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Medicine
- License
- License undefined
- Identifiers
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- RERO DOC 6377
- DOI 10.1161/CIRCULATIONAHA.106.638460
- Persistent URL
- https://folia.unifr.ch/unifr/documents/300358
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