on October 9, 2003
Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print October 9, 2003, doi: 10.1161/01.ATV.0000099880.09014.7D
Published online before print October 9, 2003, doi: 10.1161/01.ATV.0000099880.09014.7D
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Submitted on September 6, 2003
Accepted on September 26, 2003
Thrombin and Phenotypic Modulation of the Endothelium
Takashi Minami ;
From the Research Center for Advanced Science and Technology (T.M., A.S., T.K.), University of Tokyo, Tokyo, Japan, and the Division of Molecular and Vascular Medicine (S.W., R.A., W.C.A.), Beth Israel-Deaconess Medical Center/Harvard Medical School, Boston, Mass.
* To whom correspondence should be addressed. E-mail: waird{at}bidmc.haervard.edu.
Abstract--Thrombin signaling in the endothelium is linked to multiple phenotypic changes, including alterations in permeability, vasomotor tone, and leukocyte trafficking. The thrombin signal is transduced, at least in part, at the level of gene transcription. In this review, we focus on the role of thrombin signaling and transcriptional networks in mediating downstream gene expression and endothelial phenotype. In addition, we report the results of DNA microarrays in control and thrombin-treated endothelial cells. We conclude that (1) thrombin induces the upregulation and downregulation of multiple genes in the endothelium, (2) thrombin-mediated gene expression involves a multitude of transcription factors, and (3) future breakthroughs in the field will depend on a better understanding of the spatial and temporal dynamics of these transcriptional networks. This review is based in part on a Plenary Lecture at the Arteriosclerosis, Thrombosis, and Vascular Biology Conference in May 2003.
Key words: thrombin • transcription • DNA microarrays • endothelial cells
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