Troglitazone, but not rosiglitazone, inhibits Na/H exchange activity and proliferation of macrovascular endothelial cells

de Dios, Stephanie T., Hannan, Katherine M., Dilley, Rodney J., Hill, Michael A. and Little, Peter J. (2001) Troglitazone, but not rosiglitazone, inhibits Na/H exchange activity and proliferation of macrovascular endothelial cells. Journal of Diabetes and its Complications, 15 3: 120-127. doi:10.1016/S1056-8727(01)00141-6


Author de Dios, Stephanie T.
Hannan, Katherine M.
Dilley, Rodney J.
Hill, Michael A.
Little, Peter J.
Title Troglitazone, but not rosiglitazone, inhibits Na/H exchange activity and proliferation of macrovascular endothelial cells
Journal name Journal of Diabetes and its Complications   Check publisher's open access policy
ISSN 1056-8727
1873-460X
Publication date 2001-05-01
Sub-type Article (original research)
DOI 10.1016/S1056-8727(01)00141-6
Open Access Status Not yet assessed
Volume 15
Issue 3
Start page 120
End page 127
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Formatted abstract
Diabetes is associated with a high level of mortality due to cardiovascular disease resulting from accelerated coronary artery atherosclerosis. A current focus for investigation of atherosclerotic mechanisms is the vascular endothelium since physical or functional injury may represent an initiating step for atherogenesis. Thiazolidinediones (TZDs) are the newest class of drugs for the treatment of insulin resistance and its metabolic consequences; they are peroxisome proliferator-activating receptor (PPAR)-γ ligands that act as insulin-sensitizing agents. We are interested in the contribution of direct vascular actions to the clinical utility of these agents. We investigated the effect troglitazone and rosiglitazone on endothelial cell proliferation in low- and high-glucose media and further explored their action on the ubiquitous membrane transport system, the Na/H exchanger (NHE), which has been implicated in regulating the growth of vascular cells. Experiments were conducted in cultured bovine aortic endothelial cells (BAECs). Cell proliferation was assessed by cell counting, and NHE activity was determined in cells loaded with the pH-sensitive fluorescent dye, 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF-AM). Troglitazone caused a dose-dependent inhibition of endothelial cell proliferation with approximately 50% inhibition at 10 μM. Troglitazone inhibited endothelial cell proliferation with similar potency under low- (5 mM) and high-glucose (25 mM) concentrations. Rosiglitazone had no significant effect on endothelial cell proliferation at concentrations of up to 100 μM under low- or high-glucose concentrations. The NHE inhibitor, 3-metlylsulfonyl-4-piperidinobenzoyl guanidine (HOE 694), caused dose dependent inhibition of BAEC proliferation, which was independent of the media glucose concentration. Acute exposure of cells to troglitazone (10 μM) and rosiglitazone (30 μM) during recovery from acidosis showed slight but significant (P<.05) inhibition of NHE activity by troglitazone, but no significant (P>.05) effect by rosiglitazone. Exposure of cells to either drug for 24 h revealed no chronic regulation of NHE activity. Our data demonstrate that troglitazone has similar actions in endothelial cells as in vascular smooth muscle. The absence of rosiglitazone effects, a more potent PPAR-γ activator, suggests that the observed actions of troglitazone may be at least partially independent of PPAR-γ. The effects of troglitazone and rosiglitazone on endothelial cell proliferation and NHE activity, although contrasting, are consistent with a central signalling role of this transporter in cell proliferation.
Keyword Endothelial cells
Macrovascular disease
Rosiglitazone
Sodium hydrogen exchange
Troglitazone
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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