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Cardiovascular Research 2007 73(3):504-511; doi:10.1016/j.cardiores.2006.11.001
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Copyright © 2006, European Society of Cardiology

A new rat model of diabetic macrovascular complication

Céline Bouveta, Wouter Peetersb,1, Simon Moreaua,1, Denis deBloisc and Pierre Moreaua,*

aUniversity of Montreal, Montreal, Québec, Canada
bDepartment of Nephrology, University Medical Center, Utrecht, The Netherlands
cDepartment of Pharmacology, Faculty of Medicine, University of Montreal, Québec, Canada

* Corresponding author. Université de Montréal, P.O. Box 6128, Station "Centre-Ville", 2900 Edouard Montpetit, Pavillon Jean-Coutu, room 3197, Montréal, Québec, Canada H3C 3J7. Tel.: +1 514 343 6111x3313; fax: +1 514 343 7073. Email address: pierre.moreau{at}umontreal.ca

Objectives: Age-related medial calcification (elastocalcinosis) of large arteries is accelerated in diabetes and appears mainly in distal arteries. The aim was to devise a rat model of elastocalcinosis in association with diabetes to examine the hypothesis that diabetes accelerates vascular calcification experimentally.

Methods: Male Wistar rats received a high fat diet during 2 months followed by a low dose of streptozotocin to induce diabetes (D). Elastocalcinosis was facilitated by 3 weeks of treatment with warfarin and vitamin K (WVK). We started WVK treatment 1 week (D4WVK) and 4 weeks (D7WVK) after the injection of streptozotocin and in age-matched healthy rats. Measurements of hemodynamic and metabolic parameters, aortic and femoral calcium content, and immunohistochemistry for alkaline phosphatase, osteopontin, tumor necrosis factor (TNF)-{alpha}, and transforming growth factor (TGF)-TGF-β were performed.

Results: Three weeks of WVK treatment alone did not increase the calcium content in the aorta and femoral arteries. However, in the D7WVK group, femoral calcification, but not aortic calcium content, increased significantly as compared to the WVK group. This response was not observed in the D4WVK group. In femoral arteries, strong immunostaining for alkaline phosphatase and osteopontin was observed in the D7WVK group. TNF-{alpha} and TGF-β expressions were mainly localized in the adventitia of arteries from diabetic rats.

Conclusion: We have established a model of accelerated elastocalcinosis in diabetes related to its duration and localized in distal arteries. The modification of local protein expression is also in accordance with clinical data, suggesting that this model could be useful to investigate mechanisms related to this important clinical macrovascular complication of diabetes.

KEYWORDS Diabetes; Elastocalcinosis; Arteriosclerosis; Alkaline phosphatase; Osteopontin


1 Those authors contributed equally to the project.

Time for primary review 21 days


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