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(Circulation. 2006;114:1512-1521.)
© 2006 American Heart Association, Inc.

Vascular Medicine

Dimethyl Sulfoxide Inhibits Tissue Factor Expression, Thrombus Formation, and Vascular Smooth Muscle Cell Activation

A Potential Treatment Strategy for Drug-Eluting Stents

Giovanni G. Camici, BSc; Jan Steffel, MD; Alexander Akhmedov, PhD; Nicola Schafer, BSc; Jeannette Baldinger, BSc; Urs Schulz, BSc; Kushiar Shojaati, PhD; Christian M. Matter, MD; Zhihong Yang, MD; Thomas F. Lüscher, MD; Felix C. Tanner, MD

From Cardiovascular Research, Physiology Institute (G.G.C., J.S., A.A., N.S., J.B., U.S., K.S., C.M.M., T.F.L., F.C.T.) and Center for Integrative Human Physiology (G.G.C., J.S., A.A., K.S., C.M.M., T.F.L., F.C.T.), University of Zürich, Zürich, Switzerland; Cardiology (C.M.M., T.F.L., F.C.T.), Cardiovascular Center, University Hospital Zürich, Zürich, Switzerland; and Faculty of Medicine (Z.Y.), Physiology Institute, University of Fribourg, Fribourg, Switzerland.

Correspondence to Felix C. Tanner, MD, Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. E-mail felix.tanner{at}access.unizh.ch

Received May 5, 2006; revision received July 6, 2006; accepted July 28, 2006.

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- 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.

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