This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pozza, L. M. Articles by Austin, R. C. Search for Related Content PubMed PubMed Citation Articles by Pozza, L. M. Articles by Austin, R. C. Pubmed/NCBI databases Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1529.)
© 2005 American Heart Association, Inc.

Editorials

Getting a GRP on Tissue Factor Activation

Lindsay M. Pozza; Richard C. Austin

From the Department of Pathology and Molecular Medicine, McMaster University and the Henderson Research Centre, Hamilton, Ontario, Canada.

Correspondence to Richard C. Austin, Henderson Research Centre, 711 Concession Street, Hamilton, Ontario L8V 1C3. E-mail raustin@thrombosis.hhscr.org

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Atherothrombosis, defined as atherosclerotic lesion disruption with superimposed thrombosis, is the underlying cause of cardiovascular disease that accounts for the majority of deaths in North America.¹ Thrombosis at these sites is triggered by tissue factor (TF), an integral membrane glycoprotein essential for the initiation of blood coagulation.² TF-dependent procoagulant activity occurs on the surface of cells and is induced by a wide range of physiological agents/conditions, including endotoxin,³ viral infection,⁴ hypoxia,⁵ apoptosis,⁶ homocysteine,⁷ and reactive oxygen species.⁸ Furthermore, tumor cells express TF and the prothrombotic state observed in cancer patients has been largely attributed to increased TF procoagulant activity.⁹ Thus, the ability to inhibit TF-dependent procoagulant activity after plaque disruption would likely alleviate many of the acute clinical manifestations of cardiovascular disease.

See page 1737

Although TF expression is regulated in a cell-specific manner,¹⁰ the presence of TF does not necessarily correlate with procoagulant activity given that only a small proportion of TF on the cell surface is active.¹¹ Current thinking is that TF activation occurs at the cell surface when latent or "encrypted" TF is converted into an active or "de-encrypted" form.^12–14 The complex formed between de-encrypted TF on the cell surface and circulating factor VII/VIIa acts as a catalyst for the conversion of factors IX and X to IXa and Xa, respectively, thereby triggering thrombin generation. Although previous studies have demonstrated that de-encryption of TF is associated with Ca²⁺-induced changes in the distribution of cell surface phosphatidylserine,¹⁴ it is not solely dependent on these changes. Cross-linking studies . . . [Full Text of this Article]