Troglitazone stimulates repair of the endothelium and inhibits neointimal formation in denuded rat aorta

Hannan, Katherine M., Dilley, Rodney J., de Dios, Stephanie T. and Little, Peter J. (2003) Troglitazone stimulates repair of the endothelium and inhibits neointimal formation in denuded rat aorta. Arteriosclerosis, Thrombosis, and Vascular Biology, 23 5: 762-768. doi:10.1161/01.ATV.0000069210.46539.0D


Author Hannan, Katherine M.
Dilley, Rodney J.
de Dios, Stephanie T.
Little, Peter J.
Title Troglitazone stimulates repair of the endothelium and inhibits neointimal formation in denuded rat aorta
Journal name Arteriosclerosis, Thrombosis, and Vascular Biology   Check publisher's open access policy
ISSN 1079-5642
1524-4636
Publication date 2003-05-01
Sub-type Article (original research)
DOI 10.1161/01.ATV.0000069210.46539.0D
Open Access Status Not yet assessed
Volume 23
Issue 5
Start page 762
End page 768
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Objective: Vascular endothelium is emerging as a therapeutic target for atherosclerotic macrovascular disease in diabetes using oral hypoglycemic agents with pleiotropic actions. We have addressed whether the thiazolidinedione troglitazone has effects on the endothelial cell response to injury in rat aorta and its interaction with the growth response of underlying vascular smooth muscle.

Methods and Results: Repair of rat aorta after balloon catheter injury in troglitazone-treated (400 mg/kg per day by mouth) rats showed early acceleration of reendothelialization and late reduction in neointima formation. Complementary in vitro studies showed that troglitazone dose-dependently inhibited migration and proliferation of cultured macrovascular endothelial and vascular smooth muscle cells in low-glucose (5 mmol/L) and high-glucose (25 mmol/L) media. However, in endothelial cells, the inhibitory response at low (<3 μmol/L) troglitazone concentrations resulted from direct inhibition of proliferation, whereas inhibition at higher (10 μmol/L) concentrations was secondary to apoptosis and necrosis. Additional studies indicated a concentration- specific activity of troglitazone to protect endothelial cells from apoptosis.

Conclusions: Troglitazone had effects consistent with maintenance of vascular integrity and protection against mechanisms of atherosclerosis and restenosis, which may arise from a concentration-specific effect to reduce high rates of apoptosis occurring in cultured cells and repairing vessels.
Keyword Apoptosis
Endothelial cells
Reendothelialization
Troglitazone
Vascular smooth muscle cells
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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