Abstract | BACKGROUND: OBJECTIVES: METHODS:
Insulin-resistant, obesity-prone mice (KK strain) were treated with pioglitazone, placebo, or the sulfonylurea compound, glipizide, for 2.5 weeks and then subjected to photochemical injury of the carotid artery. RESULTS: KK mice have a significant increase in adiposity (7 weeks: 25.6%; 15 weeks: 34.4%; P < 0.0001) and thrombotic tendency (7 weeks: 21.2 +/- 1.9 min; 15 weeks: 13.7 +/- 1.7 min; P < 0.01) with age. Pioglitazone provided significant protection from thrombosis at both time points, prolonging the time to occlusive thrombosis by 40% and 68%, at 7 and 15 weeks of age, respectively (P < 0.05). Similarly, following a diet-challenge to promote diabetes, pioglitazone provided protection from occlusive thrombus formation (Placebo: 11.3 +/- 1.0 min; Pioglitazone: 22.3 +/- 3.9 min; P < 0.05). However, despite a salient effect of glipizide on the hyperglycemia of the mice, there was no effect on the time to occlusive thrombus formation (13.2 +/- 0.9 min, n = 4) compared with placebo-treated mice. The pioglitazone protection was paralleled by significantly lower soluble P-selectin and platelet P-selectin expression providing evidence of an antiplatelet effect. CONCLUSIONS: We conclude that pioglitazone treatment provides protection against arterial thrombosis in an obese, insulin resistant, prothrombotic mouse model.
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Authors | P F Bodary, F B Vargas, S A D King, K L Jongeward, K J Wickenheiser, D T Eitzman |
Journal | Journal of thrombosis and haemostasis : JTH
(J Thromb Haemost)
Vol. 3
Issue 10
Pg. 2149-53
(Oct 2005)
ISSN: 1538-7933 [Print] England |
PMID | 16194192
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- P-Selectin
- Platelet Aggregation Inhibitors
- Thiazolidinediones
- Pioglitazone
- Glipizide
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Topics |
- Animals
- Carotid Arteries
- Disease Models, Animal
- Drug Evaluation, Preclinical
- Glipizide
(pharmacology, therapeutic use)
- Insulin Resistance
- Mice
- Obesity
(complications)
- P-Selectin
(blood)
- Pioglitazone
- Platelet Aggregation Inhibitors
- Thiazolidinediones
(pharmacology, therapeutic use)
- Thrombosis
(drug therapy, prevention & control)
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