A new rat model of diabetic macrovascular complication.
OBJECTIVE
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-beta 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-beta expressions were mainly localized in the adventitia of arteries from diabetic rats.


CONCLUSIONS
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.
Bouvet
Céline
C
University of Montreal, Montreal, Québec, Canada.
Peeters
Wouter
W
Moreau
Simon
S
DeBlois
Denis
D
Moreau
Pierre
P
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001011:Aorta / Q000737:chemistry; D001161:Arteriosclerosis / Q000378:metabolism; D002114:Calcinosis / Q000378:metabolism; D002118:Calcium / Q000032:analysis; D003921:Diabetes Mellitus, Experimental; D003925:Diabetic Angiopathies; D005263:Femoral Artery / Q000737:chemistry; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D023421:Models, Animal; D053495:Osteopontin / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014812:Vitamin K / Q000494:pharmacology; D014859:Warfarin / Q000494:pharmacology
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D014812:Vitamin K; D014859:Warfarin; D000469:Alkaline Phosphatase; D002118:Calcium