Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hafer-Macko, C. E.
Right arrow Articles by Macko, R. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hafer-Macko, C. E.
Right arrow Articles by Macko, R. F.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 51:1957-1963, 2002
© 2002 by the American Diabetes Association, Inc.

Thrombomodulin Deficiency in Human Diabetic Nerve Microvasculature

Charlene E. Hafer-Macko1,2,3, Frederick M. Ivey2,3, Kymberly A. Gyure4, John D. Sorkin2,3, and Richard F. Macko1,2,3

1 Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland
2 Department of Gerontology, University of Maryland School of Medicine, Baltimore, Maryland
3 Baltimore Veterans Administration Medical Center - Geriatrics Research, Education, and Clinical Center, Baltimore, Maryland
4 Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland

Human diabetic neuropathy is multifactorial in etiology, with ischemia as a final common pathology. Although impaired vascular endothelial cell function in diabetic microvascular injury is established, the role of thrombomodulin (TM)-dependent protein C antithrombotic mechanism in the pathogenesis of neuropathy is unclear. This neuropathologic case-control study investigated whether vascular endothelial TM expression is deficient in peripheral nerve microvessels in diabetic neuropathy. Sural nerve biopsies from 7 patients with diabetic neuropathy and 10 with axonal neuropathy without vasculopathy were immunostained with anti-TM and anti–von Willebrand factor (vWF; an endothelial cell marker) antibodies. The proportion of TM-positive microvessels was expressed relative to total vWF-staining vessels, according to vessel caliber and regional distribution within the nerve. In diabetic nerves compared with reference controls, the proportion of TM-positive endoneurial microvessels was 15-fold lower (0.02 vs. 0.30 in diabetic nerves vs. controls, P < 0.004), and the proportion of small-caliber epineurial microvessels was 10-fold lower (0.04 vs. 0.43, P < 0.001). No TM expression was detected at the perineurium in diabetic or control nerves. We demonstrate a substantial reduction of vascular endothelial TM expression throughout human diabetic neuropathy. These findings suggest that an impaired native TM-dependent protein C antithrombotic mechanism may contribute to microvascular ischemia in the pathogenesis of diabetic neuropathy.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 NeurologyHome page
C. E. Hafer-Macko, F. M. Ivey, J. D. Sorkin, and R. F. Macko
Microvascular tissue plasminogen activator is reduced in diabetic neuropathy
Neurology, July 17, 2007; 69(3): 268 - 274.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart J SupplHome page
Authors/Task Force Members, L. Ryden, E. Standl, M. Bartnik, G. V. d. Berghe, J. Betteridge, M.-J. de Boer, F. Cosentino, B. Jonsson, M. Laakso, et al.
Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: full text: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD)
Eur. Heart J. Suppl., June 1, 2007; 9(suppl_C): C3 - C74.
[Full Text] [PDF]

Home page
 Eur Heart JHome page
Authors/Task Force Members, L. Ryden, E. Standl, M. Bartnik, G. Van den Berghe, J. Betteridge, M.-J. de Boer, F. Cosentino, B. Jonsson, M. Laakso, et al.
Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD)
Eur. Heart J., January 1, 2007; 28(1): 88 - 136.
[Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
D. W. Sommeijer, A. Beganovic, C. G. Schalkwijk, H. Ploegmakers, C. M. van der Loos, B. E. van Aken, H. ten Cate, and A. C. van der Wal
More Fibrosis and Thrombotic Complications but Similar Expression Patterns of Markers for Coagulation and Inflammation in Symptomatic Plaques from DM2 Patients
J. Histochem. Cytochem., September 1, 2004; 52(9): 1141 - 1149.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
M. A. Creager, T. F. Luscher, F. Cosentino, and J. A. Beckman
Diabetes and Vascular Disease: Pathophysiology, Clinical Consequences, and Medical Therapy: Part I
Circulation, September 23, 2003; 108(12): 1527 - 1532.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2002 by the American Diabetes Association.