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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:e34.)
© 2006 American Heart Association, Inc.

Thrombosis

Rapid Release of Active Tissue Factor From Human Arterial Smooth Muscle Cells Under Flow Conditions

Jan-Julius Stampfuss; Petra Censarek; Jens W. Fischer; Karsten Schrör; Artur-Aron Weber

From the Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Germany.

Correspondence to Artur-Aron WeberInstitut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany. E-mail weberar{at}uni-duesseldorf.de

Circulating tissue factor (TF) is an important determinant of coronary thrombosis. Among other cell types, such as monocytes, vascular smooth muscle cells (SMCs) are capable of releasing TF. When studied under static conditions, SMCs do release TF, but this process is slow and, thus, cannot explain the elevated levels of circulating TF, as observed in patients with acute coronary syndromes. The present study demonstrates that cultured human mammary artery SMCs very rapidly (minutes) release active, microparticle-bound TF when exposed to flow conditions. There was a clear log-linear correlation between the shear rate (range 10 s^–1 to 1500 s^–1) and the procoagulant activity of SMC perfusates. Flow-dependent release of TF was transient (10 minutes) and did not measurably reduce cell surface TF content. Interestingly, a time-dependent (t_1/2 30 minutes) re-exposure of releasable TF was detected after a no-flow period. These data demonstrate that SMCs may become a pathophysiologically relevant source of TF that can be rapidly released into the circulation in situations in which endothelial damage occurs and SMCs come into a close contact with the flowing blood.

The present study demonstrates that cultured human mammary artery smooth muscle cells (SMCs) very rapidly, transiently, and repeatedly release active, microparticle-bound TF when exposed to flow conditions. Thus, SMCs may become a pathophysiologically relevant source of TF that can be released into the circulation when SMCs come to close contact with the flowing blood. The re-exposure of releasable TF may result in repeated bursts of TF, which is known to be involved in cyclic variations of coronary flow after angioplasty.

Key Words: tissue factor • microparticles • vascular smooth muscle cells • flow

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