JCB logo
Quantitative Colocalization Analysis Software
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 489K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aird, W. C.
Right arrow Articles by Rosenberg, R. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aird, W. C.
Right arrow Articles by Rosenberg, R. D.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/1997//1117 $5.00
The Journal of Cell Biology, Volume 138, Number 5, , 1997 1117-1124

Article

Vascular Bed–specific Expression of an Endothelial Cell Gene Is Programmed by the Tissue Microenvironment



William C. Aird*,{ddagger}, Jay M. Edelberg*,{ddagger}, Hartmut Weiler-Guettler*, William W. Simmons§, Thomas W. Smith§, and Robert D. Rosenberg*,{ddagger}

* Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02119; {ddagger} Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215; and § Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115

The endothelium is morphologically and functionally adapted to meet the unique demands of the underlying tissue. At the present time, little is known about the molecular basis of endothelial cell diversity. As one approach to this problem, we have chosen to study the mechanisms that govern differential expression of the endothelial cell–restricted von Willebrand factor (vWF) gene. Transgenic mice were generated with a fragment of the vWF gene containing 2,182 bp of 5' flanking sequence, the first exon and first intron coupled to the LacZ reporter gene. In multiple independent lines of mice, β-galactosidase expression was detected within endothelial cells in the brain, heart, and skeletal muscle. In isogeneic transplantation models, LacZ expression in host-derived auricular blood vessels was specifically induced by the microenvironment of the heart. In in vitro coculture assays, expression of both the transgene and the endogenous vWF gene in cardiac microvascular endothelial cells (CMEC) was upregulated in the presence of cardiac myocytes. In contrast, endothelial cell levels of thrombomodulin protein and mRNA were unchanged by the addition of ventricular myocytes. Moreover, CMEC expression of vWF was not influenced by the addition of 3T3 fibroblasts or mouse hepatocytes. Taken together, the results suggest that the vWF gene is regulated by vascular bed–specific pathways in response to signals derived from the local microenvironment.

Abbreviations used in this paper: CMEC, cardiac microvascular endothelial cells; LDL, low density lipoprotein; ONPG, O-Nitrophenyl-β-D- galactopyranoside; RT, reverse transcriptase; TM, thrombomodulin; vWF, von Willebrand factor.

Please address all correspondence to W.C. Aird, Molecular Medicine, RW-663, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Tel.: (617) 667-1031. Fax: (617) 667-2913. e-mail: waird{at}bidmc.harvard.edu


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents